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Background Anesthetics, including isoflurane, depress the electroencephalogram (EEG). Little is known about the quantitative effects of isoflurane on EEG and subcortical electrical activity responses to noxious stimulation. The authors hypothesized that isoflurane would depress the results of EEG and subcortical response to noxious stimulation at concentrations less than those needed to suppress movement. Furthermore, determination of regional differences might aid in elucidation of sites of anesthetic action. Methods Ten goats were anesthetized with isoflurane, and minimum alveolar concentration (MAC) was determined using a noxious mechanical stimulus. Depth electrodes were inserted into the midbrain reticular formation and thalamus. Needle electrodes placed in the skull periosteum measured bifrontal and bihemispheric EEG. The noxious stimulus was applied at each of four anesthetic concentrations: 0.6, 0.9, 1.1, and 1.4 MAC. Results At an isoflurane concentration of 0.6 MAC, the noxious stimulus activated the midbrain reticular formation, thalamic, and bifrontal-hemispheric regions, as shown by decreased high-amplitude, low-frequency power. For all channels combined (mean +/- SD), total (-33+/-7%), delta (-47+/-12%), theta (-23+/-12%), and alpha (-21+/-6%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 0.9 MAC, total (-35+/-5%), delta (-42+/-7%), theta (-35+/-8%), and alpha (-23+/-11%) power decreased after the noxious stimulus (P < 0.001); beta power was unchanged. At 1.1 MAC only one site, and at 1.4 MAC, no site, had decreased power after the noxious stimulus. Conclusions Isoflurane blunted EEG and midbrain reticular formation-thalamus activation response to noxious stimulation at concentrations (1.1 MAC or greater) necessary to prevent movement that occurred after noxious stimulation. It is unknown whether this is a direct effect or an indirect effect via action in the spinal cord.

The behavioral and electroencephalographic (EEG) effects of intramuscular fluphenazine decanoate (Fl-D) were investigated in rats and compared with those of fluphenazine enanthate (Fl-E) and fluphenazine HCl (Fl-HCl). It was clearly observed that 1) these two depot type neuroleptics reduced open-field activity, 2) antagonized methamphetamine-induced hyperactivity, 3) inhibited the conditioned avoidance response, and 4) produced catalepsy, for a substantially long period of time (4-35 d). Although both Fl-D and Fl-E significantly inhibited muricide in olfactory bulbectomized rats and impaired rotarod performance, these effects were relatively weak in potency and short-lasting (4 h-2 d). The EEG was changed to a drowsy pattern which consisted of high voltage slow waves following the injection of Fl-D and Fl-E. Fl-D significantly inhibited the EEG arousal response to auditory stimulation, but Fl-E did not. However, neither Fl-D nor Fl-E inhibited the EEG arousal response to electrical stimulation of the midbrain reticular formation and posterior hypothalamus. These results indicate that Fl-D has the same spectrum of pharmacological activity as Fl-E, except for its longer duration of action in antagonizing methamphetamine as well as in inhibiting the EEG arousal response to auditory stimulation.

EVERAL INVESTIGATORS have observed incr ases both in epileptic-seizure threshold following alcohol administration (1-6) and in seizure probability on alcohol withdrawal after prolonged use (7-11). However, relatively little research has been devoted to alcohol's effect on seizure activity elicited in specific central nervous system (CNS) areas. Kalant et al. (12) have suggested that electrical seizure activity during alcohol withdrawal may originate in subcortical nuclei and then be propagated to and amplified by the cortex. Studies (13, 14) in which electroencephalograms (EEC) were recorded during withdrawal suggest that parts of the limbic system and midbrain reticular formation may be affected differently. The present study examines alcohol's effect on the development of seizures induced by kindling in the amygdala. Kindling involves stimulating a discrete brain nucleus, typically the amygdala, at an intensity that initially has no discernible behavioral effect. With repeated daily stimulation, however, full clonic convulsions will develop in approximately 2 weeks. Because kindled seizures are elicited by a discrete electrical stimulus to a specific brain site, the kindling paradigm offers a unique and valuable tool for studying alcohol's effects on seizure activity in the CNs. It has been demonstrated, for example, that kindled-seizure thresholds are elevated after single doses of alcohol (15), and seizures during withdrawal are intensified when kindling occurs in the amygdala prior to alcohol administration (16).

The localization of cholinergic receptors in brain synaptosomes and in synapses of the midbrain reticular formation and hypothalamic preoptic nucleus has been demonstrated by means of a horseradish peroxidase-alpha-bungarotoxin (HRP-alpha-Btx) conjugate. Only a small proportion of the total number of synapses was reactive. Axon terminals of reactive synapses contained primarily small clear vesicles, while synapses characterized by large numbers of dense core vesicles were unreactive. Toxin-binding sites were found to occur in a thickened zone of the postsynaptic surface. This procedure can be employed to study the regional distribution and localization of nicotinic receptor sites in the central nervous system.

Large lesions of superior colliculus which invade adjacent areas such as the midbrain reticular formation have been found to produce in rats a wide range of behavioral effects, including disruption of feeding, and locomotor hyperactivity in the open field. The anatomical bases of these effects were investigated with more restricted lesions of the midbrain. Feeding and motor impairments were found only after lesions that caused substantial damage to the midbrain reticular formation, not after lesions that were largely confined to the superior colliculus. In contrast, locomotor activity was increased after lesions that damaged primarily either the reticular formation or the superior colliculus. These results and other evidence suggest that there may be a localized region in the midbrain tegmentum that is concerned with aspects of feeding, whereas a wide area of the tegmentum, together with the deep layers of the superior colliculus, may be involved in the control of open-field locomotor activity.

The effects of bilateral olfactory bulb (OB) ablation on pressor and behavioral responses to stimulation of the posterior hypothalamic area (PHA) and midbrain reticular formation (MRF) were investigated in unanesthetized and unrestrained rats with chronic electrodes and arterial cannula implants. Bilateral olfactory bulbectomy induced a marked increase in emotional responses to given stimuli. A high incidence of muricide was also observed after olfactory bulbectomy. The threshold for inducing behavioral arousal and pressor response to PHA and MRF stimulation significantly decreased at 5 and 10 days after olfactory bulbectomy. The pressor responses to either PHA or MRF stimulation were markedly enhanced. The enhancement in pressor response to MRF stimulation occurred immediately after olfactory bulbectomy and persisted throughout the experiment, while that to PHA stimulation appeared gradually and reached maximum at 10 days after olfactory bulbectomy. These results suggested that olfactory bulbectomy has a great influence not only on emotionality but also on the central neural mechanisms of autonomic regulation.

Neuronal rate fluctuations in midbrain reticular formation (MRF) in chronically implanted, behaving cat were analyzed for occurrences of slow rhythmic activity (periods 6–24 s) in quiet waking and synchronized sleep (S). Appreciable rhythmicity, when compared to that resulting from randomly ordered intervals, was found in both vigilance states with rhythmic periods usually between 8 and 12 s. Fifteen MRF neurons having epochs exceeding 2 min in S, and analyzed as a group, suggest the existence of common rhythms related to the onset of S, show a significant rate decrease about 1 min before the end of S, and suggest a possible return of common rhythms relative to the end of the state.

Summary In the kindling model of experimental epilepsy, long-lasting functional changes at the synaptic structures appear to be essential for persistent seizure susceptibility. Although no remarkable morphological changes have been found at the synaptic structures, there are some neurophysiological and neuropharmacological evidences suggesting that a functional alteration in the catecholaminergic systems could be resulted following kindling and that the catecholaminergic structures may play an inhibitory role for establishing such transsynaptic changes underlying kindling. Regarding seizure generalization, two patterns of seizure generalization may be distinguished in the cortical kindling and limbic seizure. In the limbic seizure generalization, the increased connections between the limbic foci and midbrain reticular formation and/or the catecholaminergic structures seems to be important. On the other hand, functional connections between the cortical foci and generalization mechanisms, including the lower brainstem or the catecholaminergic systems, are not stronger than the limbic seizure. A longlasting functional alteration of the catecholaminergic systems that can result during kindling should be further studied in the future.

This study explores resetting of respiratory rhythm by facilitatory perturbations. The midbrain reticular formation and periaqueductal gray matter were electrically stimulated to evoke facilitation of phrenic nerve activity in nine anesthetized, vagotomized, and glomectomized adult cats. The animals were paralyzed and servo-ventilated to keep end-tidal PCO2 constant. Brief midbrain stimuli were given at various times in the respiratory cycle and the times of onset of rescheduled breaths after stimulation were measured. A plot of phase resetting as a function of stimulus strength and time of delivery defined a helicoid surface. The axis of this helicoid identified a unique stimulus which, when given at the inspiratory-expiratory transition, resulted in unpredictable resetting of respiratory rhythm. This stimulus had a strength that was intermediate to that which identified types 1 and 0 resetting. In one experiment, the singular stimulus often initiated a breath having prolonged inspiratory activity; resumption of the normal rhythm was delayed significantly (P less than 0.01). We conclude that the dysrhythmias observed in this study represent the respiratory oscillator''s phase singularity.

Attack by a cat on a rat was elicited by electrical stimulation of the ventral parabrachial nucleus or the paralemniscal pontine reticular formation. The attack was quiet and it differed from similar behavior elicited at other sites in that the cat not only bit the rat but struck it with its paw. Horseradish peroxidase was deposited at the attack sites. Cells sending projections to the attack sites were located in gyrus proreus, anterior, central, and medial amygdala, the bed nucleus of the stria terminalis, lateral, dorsal and perifornical hypothalamus, as well as the central gray matter, superior colliculus, midbrain reticular formation, locus coeruleus, nucleus of the lateral lemniscus, and nucleus interpositus. Additional sites of cells of origin appeared with less regularity. This distribution of sites correlates well with the sites from which attack can be elicited or modulated.

Afferent sources from meso-diencephalon to n. raphe magnus (RM) were examined by the HRP method. Following HRP injection into RM, HRP-labeled cell clusters occurred in: (1) n.linealis rostralis; (2) ventrocaudal part of n.parafascicularis; (3) zona incerta; and (4) midbrain reticular formation. As a rule, the axons from (1) and (4) mainly terminate within RM, while those from (2) and (3) seem to project to the inferior olive (IO) as well as RM. The functional significance of these nuclei is briefly discussed.

A combined push-pull cannula and microwire unit recording device was developed to study brain unit discharge within the field of perfused agents during sleep in behaving cats. KCl perfusion increased pontine reticular formation (PRF) unit discharge and protein concentrations in the perfusate. Simultaneous midbrain reticular formation unit recordings showed either increased or decreased rates. By contrast, chloramphenicol perfusion suppressed PRF unit discharge, particularly during sow-wave sleep (SWS) and SWS-REM transition periods. Unit recordings were stable for several hours during perfusion experiments. This method allows simultaneous study of (i) unit discharge within a chemically stimulated brain region, (ii) agents released in the perfusate, and (iii) behavioral and remote electrophysiologic responses.

Multiple-unit activity (MUA), recorded simultaneously from many brain areas, was used to detect the existence ahd location of "target sites" for ethanol action in rabbits with chronically implanted electrodes in 14 areas. Each of 12 rabbits received intraperitoneal injection of 300, 600, 900, and 1200 mg/kg of 20% ETOH and a saline control injection given in random order with at least a 4-day interval between injections. Large amounts of MUA data, recorded continuously for a 2-min pre-injection control period and a 15-min post-injection period, were quantified by a sensitive and unique technique. MUA changes did not correlate with alcohol-induced changes in the corresponding EEG for the same locus. Whereas visual inspection of the EEG did not disclose any regional differences in response to ethanol, both temporal and topographical differences in ethanol effect on MUA were observed. There were 14 histologically verified brain areas with adequate sample size for statistical evaluation of MUA response. At high doses, all brain areas were affected. Included among the brain areas which were least affected by low doseas were the caudate nucleus, septum, fornix, and medial forebrain bundle. Those areas that met the criteria for target sites of responding quickly (less than 5 min) to low doses (300 mg/kg) were: cerebellar cortex, cerebral cortex, hippocampus, lateral and medial geniculate nuclei, midbrain reticular formation, and pyriform cortex. In conjunction with the preliminary study [Brain Res. 70, 361 (1974], the data indicate that the most ethanolsensitive tissue is found in the various kinds of cortex, cerebellar and cerebral (both paleocortex and neocortex).

Effects of systemic administration of a single dose (50 mg/kg) of ethosuximide (ESM) on extracellularly recorded thalamic (nucleus centralis lateralis, CL; nucleus reticularis, RE) and cortical neurons and on cortical EEG activity of acute cats, have been studied. In intact animals ESM led to: (a) desynchronization of cortical EEG activity; (b) reduction of cortical recruiting responses to 6 Hz stimulation of nucleus centralis medialis (CeM); (c) increased firing rate of CL units; and (d) reduction of incremental responses (IRs) of CL neurons to CeM stimulation. In midbrain reticular formation (MRF)-lesioned animals, ESM induced: (a) reduction of cortical spindle waves; (b) increment of their intraburst frequency; (c) reduction of the IR of CL neurons to 3 and 6 Hz CeM stimulation; (d) shortening of the inhibitory period following each response; and (e) no increment of spontaneous firing rate of CL units. Moreover, ESM led to important changes in the spontaneous activity of RE neurons: spike barrages, typical of these neurons in MRF-lesioned animals, became less frequent and of longer duration, being also constituted by longer interspike intervals. However, responses of RE neurons to low frequency CeM stimulation, when present, did not show any incremental phenomenon and appeared unchanged after ESM. Responses of cortical neurons to paired stimuli, applied with different interstimulus intervals, to nucleus ventralis posterolateralis or in animals with isolated cortex, to subcortical white matter, disclosed a reduction of the cortical inhibitory period following the response to the conditioning stimulus. These data suggest that ESM exerts a moderate diffuse anti-inhibitory action at both cortical and thalamic levels and an activating effect on MRF, which could also be accomplished through disinhibition. The reduction of the inhibitory phases in thalamic nuclei would alter spontaneous intrathalamic synchronizing mechanisms, leading to a decreased effectiveness of thalamocortical volleys, which are believed to be fundamental for the appearance of cortical spike and wave discharges. This hypothesis would therefore explain the specific efficacy of ESM against absence seizures.

Spontaneous firing of midbrain reticular formation (MRF) neurons was recorded extracellularly in chronically implanted, behaving cats during steady and transitional states of the sleep-waking cycle. Physiological identification of receiver and/or projection MRF neurons was achieved through orthodromically elicited discharges. Discharge rates of MRF neurons were more than double in waking (W) and active sleep (D) without phasic motor events, as compared to synchronized sleep (S). During behavioral states associated with EEG activation, the increased firing was essentially due to cells exhibiting high discharge rates, located at relatively ventral levels of the midbrain core. MRF neurons with identified rostrally projecting axons were more active during W and D states; their discharge rates were significantly higher than those of caudally projecting cells. The discharge patterns of MRF neurons increasing their firing rates from S to W and D were of the tonic type. First-order analyses showed a negligible proportion of both very short and long interspike intervals in all states, large interval density around the mode especially in W and D, and the smallest variation coefficients in W. Rhythmic firing with a period near the modal interval was detected during W by autocorrelations. The increase in firing rate of MRF neurons from S to W or D took place before overt EEG desynchronization and behavioral manifestations that define stable W or D states. In our sample a statistically significant increase in discharge rate was found about 15 s before the end of S sleep epochs that developed into awakening. The differences between discharge features of MRF neurons during waking and sleep states and those of neurons in other brainstem reticular fields are emphasized. Taken together, these data support, at a cellular level, Moruzzi and Magoun's concept of a rostral reticular substrate that gives rise to impulses leading to tonic activation of the thalamocortical systems.

This study examined the effects of ethanol on photic evoked potentials recorded from the dorsal lateral geniculate nucleus (LGN) and midbrain reticular formation (MRF) of chronically implanted albino rats. Animals were given intraperitoneal injections of saline, or of 0.5, 1.0, 1.5 or 2.5 g ethanol/kg body weight on separate days. Evoked potentials were recorded at 5, 20, 40 and 60 min following injection. An early positive component recorded from each structure was depressed in amplitude by only the 2.5 g/kg alcohol dose, while the succeeding negative component was depressed by both the 1.5 and 2.5 g/kg doses. Latencies of both early components in each structure were increased by the 1.5 and 2.5 g/kg alcohol doses. Alcohol doses of 1.0-2.5 g/kg depressed the amplitude of a later positive component in the LGN (latency of 78 msec), but latency was not altered. In contrast, a late positive component in the MRF (latency of 150 msec) was both decreased in amplitude and increased in latency by only the 2.5 g/kg dose. These results on subcortical structures are discussed in relation to alcohol's effects on cortical evoked potentials.

Extracellular investigations on the activity of 269 caudate neurons during electrical stimulation of the midbrain reticular formation were carried out during chronic experiments on cats. Stimuli of different sensory modalities were used: auditory, mechanical, and visual. A response was observed to both reticular and peripheral stimulation in single neurons. The former produced an orthodromic response in 53% of caudate neurons, notable for its high probability of occurrence. A total of 23% of caudal neurons responded to this type of stimulation and application of stimuli of a single modality, while 14% responded polymodally. An excitatory response pattern prevailed during all types of stimulation. By applying twin stimuli to 100 caudate neurons, a capacity for interaction between reticular and acoustic inputs was discovered. Interaction was similarly observed in neurons which had reacted neither to separate application of both stimuli nor to either of the stimuli in isolation.

The experiments reported here show that facilitation of late components of the electrically evoked visual cortical response by electrical stimulation of the midbrain reticular formation in the cat depends on nicotinic cholinergic receptors and not on muscarinic receptors that mediate the arousal reaction. Facilitation could be elicited by stimulation of areas ranging from pons to diencephalon (maximally from the central and paralemniscal tegmental fields of the midbrain) and employed a pathway traversing the intralaminar thalamic nuclei. In contrast to the effects of this reticulocortical pathway, little facilitation was obtained from the locus ceruleus, the dorsal raphe nucleus or the medial forebrain bundle through which these two monoaminergic pathways project to the cerebral cortex.

The present study was performed in an attempt to elucidate the possible neural networks and their functional modification by progesterone among estrogen and progesterone effective brain areas for lordosis behavior of the rat. Single and multiple unit activities were recorded in the medial preoptic area (MPO), dorsomedial thalamic nucleus (MD), interpeduncular nucleus (IP) and ventral part of midbrain reticular formation (MRF), and single or train pulse stimulation was applied to the MPI, MD, IP, MRF, caudate-putamen (CP), habenular nucleus (HB), dorsal hippocampus (HPC), medial and lateral septum (m- and 1-SEPT) and lateral amygdala (1-AMYG). Unit activity was recorded under urethane anesthesia in ovariectomized rats pretreated with estrogen or with estrogen and progesterone. MPO units showed facilitatory responses to stimulation in the MRF, HB and 1-SEPT, and inhibitory responses to stimulation in the MD, HPC, m-SEPT and 1-AMYG in ovariectomized estrogen-primed rats. CP stimulation inhibited the MD unit activity. Stimulation in the IP had no effect on the MPO or MD units, while the IP units were affected by stimulation in the MPO, MD, CP and HB. MRF unit was accelerated by the MD and CP and inhibited by the MPO stimulation. In the ovariectomized, estrogen and progesterone-treated rat, the MPO unit responses to the MRF and MD stimulation, and the MD unit responses to the MRF and CP stimulation were different from those in the rat with only estrogen treatment. In addition, in the ovariectomized estrogen-primed rat, local application of progesterone to the MD prevented the inhibitory effect of the MD on the MPO unit. Progesterone, when given to the stimulated brain area, accelerated the MPO unit which was activated by the MRF stimulation, and inhibited the MD neuron which was inhibited by the CP stimulation. Multiple unit recordings showed similar results. Moreover, multi-unit activity in the HB and IP was elevated following a systemic progesterone application. On the basis of these results, the possible neural networks in the brain which participate in the lordosis control mechanisms are discussed.

The local cerebral metabolism on glucose (l-CMRg) was evaluated in animals given methylphenidate (15 mg/kg) in order to investigate possible mechanisms of action of the drug. Significant increases in l-CMRg (p greater than 0.05) were found in the globus pallidus, entopeduncular nucleus, substantia nigra, subthalamic nucleus, inferior olive, red nucleus, lateral cerebellar cortex, ventral lateral nucleus of the thalamus and the midbrain reticular formation. Significant decreases (p greater than 0.05) in l-CMRg were found in the motor cortex. These results suggest possible mechanisms for methylphenidate's action in attention deficit disorders.

This research was a study, using acutely prepared rabbits, of neuronal responsivity in 7 hippocampal layers to electrical stimulation of the 3 primary input structures (entorhinal cortex, septum, and midbrain reticular formation). For each stimulus/response site, we determined the minimal stimulus intensity required to evoke a threshold response (≶ X ± 2 SD of the discharge rate immediately prior to stimulation). For all stimulus/response site combinations, the threshold voltage was low (range of 0.17 to 0.45 volts), and a threshold response was easily obtained (range of 60 to 100% of the trials). The predominant response was excitatory, but depression sometimes occurred (up to 20% incidence). Areas that never showed depression were the hippocampal and dentate molecular layers and the subiculum. The high incidence of low threshold, excitatory responses in all layers to all 3 kinds of input indicates that the hippocampus is very sensitive to diverse inputs and that excitatory input is readily distributed throughout all layers. A second phase of the research was a test of ethanol (0.8 gm/kg) influence on the evoked unit responses. Ethanol elevated threshold for all pairings. Regional differences were clearly established with brainstem reticular formation stimulation, in which threshold after ethanol was elevated more in the hippocampal molecular layer and, to a lesser extent, in the dentate granule cell layer.

The origins of the serotonergic projections to the spinal cord in the rat were determined by employing the retrograde cell marker HRP coupled with the unlabeled antibody, peroxidase-antiperoxidase immunocytochemical method of Sternberger. Large numbers of stained neurons (greater than 70%) in the medullary raphe nuclear complex were found to contain both HRP retrogradely transported from the spinal cord and positive 5-HT staining. These serotonergic cell groups, including the nucleus raphe obscurus, raphe pallidus, raphe magnus, and the ventral parts of the reticular formation, project to all spinal cord levels. In addition, some neurons contained HRP granules, but were unstained for 5-HT, suggesting that they may contain other non-serotonergic neurotransmitters. More rostrally in the midbrain reticular formation, many 5-HT neurons were found to have projections exclusively to the cervical spinal cord. These findings indicate that the descending serotonin inputs to the spinal cord originate not only from the serotonergic neurons located in the medullary raphe complex, but also from other new sources located in the central gray and reticular formation of the midbrain.

The afferent fiber connections to the interpenduncular (IP) complex were demonstrated by the retrograde axonal transport of horseradish peroxidase (HRP) in cats. The HRP was injected into each nucleus of the IP complex, that is the central nucleus (IPC), the paramedian nucleus (IPP), the apical nucleus (IPA), and the posterior nucleus (IPN) including the outer division (IPO) and the inner division (IPI), and surrounding areas of the IP complex, using a ventral or dorsal surgical approaches. Most of the labeled neurons were in the medial habenular nucleus (MH) and each of the sub-nuclei of the IP complex was related to a specific part of the MH. Thus, the mediodorsal part of MH projected to the IPC, the medioventral part of MH projected to the IPI, the laterodorsal part of MH projected to the IPA, and the lateroventral part of MH projected to the IPP and the IPO. There were a few labeled cells in the accessory dorsal tegmental nucleus, the nucleus raphe dorsalis (RD), the nucleus centralis superior, the nucleus of the locus coeruleus, the gray matter of the floor of the fourth ventricle, and the nucleus of diagonal band of Broca, but there were no obvious patterns in the projections of these nuclei to the different sub-nuclei of the IP complex. When the area of the HRP injection involved the midbrain reticular formation adjacent to the IP complex and the nucleus reticularis tegmenti pontis (RT) but not the IP complex itself, there were many labeled cells in the lateral habenular nucleus and the medial and lateral mammillary nuclei, but there were no labeled cells in the medial habenular nucleus.

The occurrence of slow negative potential changes in the lateral geniculate nucleus of the cat in response to stimulation of the midbrain reticular formation was studied. A method for distinguishing all-or-nothing from graded potentials in the presence of noise is described. Graded potential changes were obtained in the conscious and anesthetized states. All-or-nothing potential changes were obtained in the anesthetized animal only at times of spontaneous all-or-nothing waves (similar to ponto-geniculo-occipital waves). All-or-nothing waves could also be elicited in both lateral geniculate nuclei when a transection was made between the lateral geniculate nucleus and the stimulating site in the midbrain reticular formation on one side; this suggests the existence of a descending pathway to the ponto-geniculo-occipital generator in the pontine tegmentum. All-or-nothing waves could also be evoked in both lateral geniculate nuclei after a transection caudal to the stimulating site on one side. This suggests either that such stimulation excites a pathway which crosses to the other side of the brain and then descends to the ponto-geniculo-occipital generator or that the all-or-nothing mechanism is more rostral and stimulation of the midbrain reticular formation either excites this region directly or excites pathways projecting to this region.

Transection of the ventral central grey and surrounding midbrain tegmentum in anaesthetized lactating rabbits caused repeated milk ejections which, on comparison with the effects of i.v. infusions of synthetic oxytocin, synthetic arginine-vasopressin or a mixture of the two, were attributed to continuous release of 1·25–2·5 mu. oxytocin/min, although it is not known whether lesser amounts of vasopressin might also have been released. It is suggested that the ascending midbrain reticular formation, which is known to project rostrally through this region, controls the central inhibition of oxytocin release via the previously described septo-hippocampo-subicular route to the hypothalamus. J. Endocr. (1986) 109, 405–409

The subcortical nuclear groups projecting to the nucleus reticularis tegmenti pontis (NRTP) were studied in pigmented rats with the aid of the retrograde horseradish peroxidase (HRP) technique. Small iontophoretic injections of HRP were placed in the medial regions of the NRTP, an area that has been shown in several species to be involved in eye movements. Other large injections in the NRTP or small injections placed just outside the nucleus were used to clarify the projections to the NRTP. Results indicate that the NRTP receives afferents from visual relay nuclei, including the nucleus of optic tract, the superior colliculus, and the ventral lateral geniculate nucleus; oculomotor-associated structures including the zona incerta, the H1 and H2 fields of Forel, the nucleus subparafasciculus, the interstitial nucleus of Cajal, the visual tegmental relay zone of the ventral tegmental area of Tsai, the mesencephalic, pontine, and medullary reticular formations, the nucleus of the posterior commissure, and a portion of the periaqueductal gray termed the supra-oculomotor periaqueductal gray; cerebellar and pontomedullary nuclei, including the superior, lateral, and medial vestibular nuclei, the deep cerebellar nuclei, and NRTP interneurons, and nuclei related to limbic functions including the lateral habenula, the mammillary nuclei, the hypothalamic nuclei, the preoptic nuclei, and the nucleus of diagonal band of Broca. A surprisingly large number of afferents to the medial regions of the NRTP arise from visual- or eye-movement-related nuclei. The projection from the nucleus of the optic tract (NOT) confirms previous anatomical and physiological studies on the pathways involved in horizontal optokinetic nystagmus, but the number of NOT afferents is small in relation to other areas potentially related to visuomotor pathways such as the zona incerta, ventral lateral geniculate nucleus, fields of Forel, perirubral area, and subparafasciculus. The NRTP may also relay information related to vertical visuomotor reflexes (e.g., vertical optokinetic nystagmus) given the strong projections from the medial terminal nucleus of the accessory optic system, visual tegmental relay zone, supra-oculomotor periaqueductal gray, interstitial n. of Cajal, and midbrain reticular formation. The presence of significant NRTP projections from the superior colliculus and the mesencephalic and pontine reticular formations suggests that these nuclei may provide the pathways for the noted saccade-related activity of NRTP neurons. In addition, projections from the vestibular nuclei were found that provide the anatomical basis for head velocity signals recorded in NRTP neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of benzodiapines administered by the intraperitoneal route on PGO firings and multiple unit activity in the midbrain reticular formation in chronic cat preparations were investigated at various levels of consciousness. Changes in the sleep-wakefulness cycl e induced by direct injection of benzodiazepines into the reticular formation were also investigated. Benzodiazepines markedly decreased multiple unit activity in the midbrain reticular formation during each stage of sleep, but had little effect during behavioral and EEG arousal. Benzodiazepines did not affect PGO firing rate, but attenuated all increase of multiple unit activity following PGO firings. The bilateral injection of benzodiazepines into the midbrain reticular formation induced an increase of arousal and a decrease of slow wave sleep, but did not change the amount of paradoxical sleep. It is concluded that benzodiazepines show a mixture of depressant and facilitatory effects, which seem to vary with the state of consciousness of the animal.

The terminal nuclei of the accessory optic system receive a dense fiber projection from the contralateral retina and have recently been implicated in visuo-vestibular aspects of oculomotor function. The present anatomical study, based on anterograde tracer experiments with 3 H-labeled amino acids or horseradish peroxidase, provides evidence for a diverse set of non-retinal inputs to the accessory optic nuclei arising in both the neocortex and the brainstem. Corticofugal fiber projections to the terminal nuclei originate in several areas of the visual cortex; those from the medial Clare-Bishop area may be especially dense. Subcortical inputs to the terminal nuclei include fiber projections arising in ( a ) the pretectal region; ( b ) the ventral mesencephalon, probably including the substantia nigra; and ( c ) more dorsal or caudal parts of the mesencephalic reticular formation. The source of the pretectal projection to the terminal nuclei appears to be the nucleus of the optic tract or the underlying posterior pretectal nucleus. Fiber projections from the ventral mesencephalic tegmentum were labeled by injections infiltrating the substantia nigra, but these deposits all involved, at least marginally, either interstitial cells of the transpeduncular limb of the accessory optic tract or the perinigral tegmentum. The part of the midbrain reticular formation giving rise to an accessory optic projection was not precisely delimited, but it appears to lie outside the substantia nigra proper. Although these afferent projections to the accessory optic nuclei appear individually to be much weaker than the input from the contralateral eye, their presence clearly suggests that transmission of visual information through the terminal nuclei may involve a complex modulation of retinal input by non-retinal pathways.

The pathway of the blink reflex, elicited by auditory stimulation, was investigated electrophysiologically. The reflex was recorded as microvibrations of the eyelid and was named the auditory-evoked eyelid microvibration (AMV). Pharmacophysiological studies suggest that AMV is closely related to the midbrain reticular formation and studies of electrical lesions in the midbrain reticular formation support this. Lesions in several parts of the central nervous system provide evidence that the inferior colliculus has an important role in AMV, and the cerebral cortex may have an inhibitory influence. Studies of brainstem transections indicate that the reflex pathway of AMV exists between the lower midbrain and the upper medulla. Because of its ease and simplicity, AMV is believed to be a useful test for evaluation of the function of the brainstem.

In order to elucidate the mechanisms and the sites of action of the negative feedback of corticoids in the regulation of ACTH secretion, the effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact rats and in 11 experimental groups. These included animals with partial anterior, anterolateral, posterolateral, posterior and small posterior deafferentations as well as bilateral lesions in the medial forebrain bundle (MFB), fasciculus longitudinalis dorsalis (FLD), medial and lateral midbrain reticular formation (MRF) and in the ventrolateral pons. In rats with posterior hypothalamic deafferentation the degree of the inhibitory effect of dexamethasone was much smaller than that in intact animals. In animals with lesions in the FLD and MRF, dexamethasone also produced a reduction in the suppression of the response, though the difference was not significant. Bilateral lesions in the MFB and MP have on the other hand very significantly enhanced the effect of the negative feedback of dexamethasone when compared to intact rats. These data would indicate that hypothalamic deafferentations and brain lesions may change the sensitivity of the hypothalamus for the feedback control of corticoids and that there exist two antagonistic systems, an inhibitory and a facilitatory, in the brain which mediate this effect.

Electrographic effects of isoflurane (Forane) on the CNS were evaluated in chronic and acute experiments. In cats with chronically implanted electrodes, EEG activity was recorded from the cortex and from selected subcortical structures. First changes during inductions of anaesthesia were observed in the structures of the specific somato-sensory system, followed by high voltage spikes in the limbic structures. Continuous hypersynchrony in all leads developed simultaneously with onset of anaesthesia and persisted or developed further into intermittent hypersynchrony during maintenance. Upon termination of inhalation of isoflurane, return to control EEG patterns and behavioural arousal occurred within seconds. In acute preparations, evoked responses recorded in the specific somato-sensory pathways following forepaw stimulation were only slightly affected, but such responses were markedly depressed or abolished in the diffuse reticulo-thalamic activating system.

Experiments were conducted on urethane-anesthetized hooded rats to test the hypothesis that reticular activation facilitates synaptic transmission through the lateral geniculate nucleus by a mechanism of disinhibition via maintained I-cell firing. The tests consisted of determining whether or not electrical stimulation of the midbrain reticular formation would still enhance the postsynaptic r1-wave of the mass potential evoked by an optic tract stimulus, in two situations in which the I-cells are apparently silent. (i) It appeared that bilateral enucleation abolished all the maintained firing of I-cells. However, in going to the enucleated state, conditioning reticular stimulation did not become ineffective. Therefore the reticular enhancement of the r1-wave in single-shock (to optic tract) experiments is not due to disinhibition via maintained firing of I-cells. (ii) For the sample of I-cells recorded there was a silent period between the end of the early firing and the beginning of the late firing evoked by a tract stimulus. Reticular stimulation applied after this early I-cell firing had ceased was found to enhance the r1-wave evoked by a second tract stimulus applied before the late I-cell firing had begun, contrary to the hypothesis. Furthermore, whereas the reticular enhancement in single-shock experiments was essentially unaffected by enucleation, the enhancement produced by reticular stimulation applied between the tract stimuli in two-shock experiments could be greatly reduced by enucleation. Therefore the mechanisms underlying these two reticular enhancement phenomena differ at least in the role played by the retinal input.

Local cerebral glucose utilization was measured in rats during nitrous oxide and pentobarbital anesthesia, using the 2-[14C]-deoxyglucose method. During nitrous oxide anesthesia, 67%, marked heterogeneity of glucose utilization was observed. During pentobarbital anesthesia (30 mg/kg), glucose utilization decreased, the decrease being pronounced in the structures where glucose utilization was high during nitrous oxide anesthesia. During combined use of nitrous oxide and pentobarbital (30 mg/kg), with an electroencephalogram (EEG) consisting of 4-6 Hz wave super-imposed by 10-15 Hz wave, glucose utilization was higher in many brain structures, including the midbrain reticular formation, than that observed during pentobarbital (30 mg/kg) anesthesia alone. With pentobarbital, 125 mg/kg, the EEG became nearly flat and a dose-related decrease in glucose utilization was observed in the cerebral cortices and inferior colliculus but not observed in any other structures. During the combined use of nitrous oxide and pentobarbital (125 mg/kg), the EEG was nearly flat, and no statistically significant differences in glucose utilization were observed as compared with those during pentobarbital (125 mg/kg) anesthesia in any of the structures examined. The results suggest that nitrous oxide and pentobarbital affect local cerebral glucose metabolism differently and that nitrous oxide acts as cerebral metabolic stimulant in the presence of cortical function during pentobarbital anesthesia.

The amplitude of anterior neocortical EEG slow-waves (0.5–4Hz) measured during quiet waking, drowsy (WS) and synchronized sleep (S) states showed slow rhythmic oscillations in WS and S similar to those previously reported in midbrain reticular neurons (periods of 8–12 s). Abrupt changes in slow rhythms of unit discharge was reflected by similar changes in the amplitude of EEG slow-waves. Analyses on grouped data from many WS → S transitions showed no common phase relation between oscillations of EEG slow-wave amplitudes prior to S onset, but showed signs of a common phase relationship after. These findings, together with a significantly lower EEG synchronization level just before S onset in grouped data, suggest that the beginning of S is phase-related to oscillations of slow-wave amplitudes in WS.

The effect of cadralazine, a new antihypertensive agent, were studied on the central nervous systems in experimental animals. Oral administration of 0.5 mg/kg or more of cadralazine depressed spontaneous motor activity and enhanced electroshock-induced convulsions in mice. The drug produced flush on the tail or ears at 0.5 mg/kg, p.o. or more and enhanced respiratory movement at 5.0 mg/kg, p.o. or more in rats. At 2.5 mg/kg, p.o., cadralazine prolonged the thiopental-sleeping time and inhibited methamphetamine-induced hypermotility as well as acetic acid-induced writhing in mice. Pretreatment of naloxone, however, failed to antagonize this inhibitory effect on acetic acid-induced writhing. Cadralazine at 5.0 mg/kg, p.o., lowered body temperature in rats. This same dose antagonized tremorine-induced behaviors in mice. Cadralazine at a dose of 1.0 or 5.0 mg/kg, i.v., had no effect on the spontaneous EEG pattern and the threshold of arousal EEG response induced by electrical stimulation to the midbrain reticular formation in rabbits. Even at a dose as large as 100 mg/kg, p.o., the drug showed no significant effect on the following effects: conditioned avoidance response in rats, spinal reflex in cats, tail pinch-induced pain in mice, and somatic function in the inclined screen or in the traction test in mice. In conclusion, cadralazine, having no passage through the blood-brain barrier, showed several pharmacological actions on behaviors. These actions are considered to be derived from its vasodilative properties and were qualitatively similar to those of hydralazine.

Direct projections to the pretectum and the midbrain reticular formation from auditory relay nuclei in the lower brainstem were examined by the retrograde and anterograde tracer methods in the cat. After horseradish peroxidase (HRP) injection into the pretectomesencephalic reticular region (Pt-MRF), which includes caudoventral regions of the pretectum and rostrodorsal regions of the midbrain reticular formation, labeled neurons were seen in the dorsal nucleus of the lateral lemniscus (DLL), the pericentral (PC) and external (EN) nuclei of the inferior colliculus (IC), the rostral process of IC (RP) and the nucleus of the brachium of IC (NB); no labeled neurons were found in the main laminated portion of the central nucleus of IC. Subsequently, tritiated leucine was injected into DLL, EN, RP or NB for autoradiographic fiber tracing. After injection into DLL or EN, terminal labeling was confined to the ventral portions of the anterior pretectal nucleus. After injection into RP or NB, heavy terminal labeling was observed in the midbrain reticular formation, extending dorsally into the anterior pretectal nucleus. Thus, 3 sectors are distinguishable in Pt-MRF in terms of termination of fibers from the midbrain auditory relay nuclei; the dorsomedial, intermediate or ventrolateral Pt-MRF sector receives fibers arising from DLL, RP or NB, respectively. Fibers from EN terminate only in the dorsal portion (pretectal regions) of the intermediate sector.

To investigate the functions of neurons in the ventral tegmental area, recordings were made of the activity of 257 single neurons in this area in the behaving monkey. Four main types of neuronal response were found in the ventral part of the tegmentum. First, neurons with activity phasically related to mouth or arm movements were found. Most of these were located relatively far lateral, close to the junction of the midbrain reticular formation with the zona incerta, or were in the substantia nigra, pars reticulata. Second, neurons were found which responded differentially in a visual discrimination task on trials on which the monkey had to initiate a licking response compared with trials on which he did not, and which also altered their firing rate tonically while mouth movements were being made in other situations (differential motor neurons). These were found mainly in the midbrain reticular formation, consistent with the view that populations of neurons in these regions are involved in the execution of movements. Third, neurons which also responded differentially in the visual discrimination task, but did not respond when the same movements were made in other situations, were found in the ventral tegmental area, in a region medial to and in some cases immediately dorsal to the substantia nigra pars compacta. Fourth, neurons which responded to cues such as a tone which enabled the monkey to prepare for performance on each trial of the visual discrimination task were found in the ventral tegmental area close to the midline. These third and fourth types of neurons were thus found in the region where neurons of the mesocortical and mesolimbic pathways are located. Their responses are similar to those of neurons found in the striatum, and it is suggested that they are important in enabling the animal to prepare for and then to engage in particular behavioral responses.

Autoradiography with [14C]2-deoxyglucose was used to examine the functional activity of the rat brain during long- and short-term habituation of the acoustic startle reflex. Long-term habituated rats, when compared to short-term rats, showed an enhanced metabolic activation of the auditory system, with the exclusion of thalamocortical levels. Regional metabolic increases were also located within the cerebellum and its major input-output structures. In contrast, the midbrain reticular formation and its ascending thalamocortical activating system showed a widespread metabolic suppression. The findings provide the first map of structures in a mammalian brain with learning-related metabolic alterations dependent on long-term habituation.

Eye movements and electroencephalographs (EEG) were recorded in intact rabbits during an optokinetic test. The animals were exposed to pure tone noise (85 dB at 4000 Hz), impulse noise (159 dB), and vibration directed at the abdomen (amplitude 0.9 mm at frequencies of 40, 80, and 120 Hz). The velocity of optokinetic nystagmus (OKN) significantly increased with these stimuli. The increase seen with vibration was greater than the noise-induced increase. The response was strongest when noise and vibration were combined. The increase in OKN induced by vibration was successive and dependent on frequency. The increase was weakest during exposure to vibration at 40 Hz and strongest at 120 Hz. EEGs of the dorsal hippocampus, amygdaloid complex, midbrain reticular formation, and frontal motor cortex were all activated during noise and vibration exposure, but activation of the hippocampal EEG was the most closely related to the increase in OKN. Combination of the different stimuli indicated that their interaction could not be predicted on the basis of responses to single stimuli, and, in most cases, the result was indifference due to the high alerting effect of vibration alone. The findings can be related to the non-specific dizziness found in aerospace workers exposed to excessive noise and vibration.

Extracellular activity of single units, simultaneously recorded in cortex, thalamus, and midbrain reticular formation was investigated during feline generalized penicillin epilepsy. The firing activity of neurons recorded in the cortex was invariably and consistently enhanced in coincidence with the positive peak and the positive-negative transient of the “spike” of the spike and wave complex, and it was greatly decreased during the wave. In the nonspecific thalamic nuclei three classes of neurons were identified according to their patterns of activity during the spike and wave complex: (i) neurons behaving like cortical units, (ii) neurons with enhanced firing activity during the wave and a decreased activity during the “spike,” and (iii) unmodified neurons. In the nucleus lateralis posterior neurons of the third class were not found. Most midbrain reticular neurons could be classified in the same three classes of the nonspecific thalamic nuclei; however, 11% of those units increased their activity 20 to 30 ms earlier than did the cortical units (class IV). Investigation of the activities of all these neuronal populations immediately prior to a spike and wave discharge showed that the rhythmic cycle of excitation-inhibition commenced earlier in the cortical neurons than in any other subcortical neuron. Moreover, there were some nonspecific thalamic neurons of class II with an inhibitory phase exactly coincident with the activation of class IV midbrain reticular neurons. These data suggest (i) a leading role of cortical neurons in initiating and maintaining a spike and wave burst; (ii) the involvement of a corticothalamocortical circuit in timing the bursts, and (iii) an accessory reticulothalamic loop also involved in regulating the intraburst frequency of the spike and wave complex.

The efferent connections of the septum in the pigeon were studied with the use of anterograde (3H-leucine autoradiography) and retrograde (horseradish peroxidase histochemistry) transport methods. It was observed that the dorsal septum projects to the lateral hypothalamus, portions of the periventricular hypothalamus, dorsomedial thalamus and midbrain reticular formation. Fibers from the ventral half of the septum (i.e., nucleus of the diagonal band) project to medial and lateral sectors of the hypothalamus, dorsomedial thalamus, lateral habenular nucleus and midbrain tegmentum. In addition, fibers originating from this region also project to the hippocampal and parahippocampal cortices.

Experiments were performed to evaluate the effects on the levels of aspartate, GABA and glutamate in the periaqueductal central gray matter, hypothalamus, midbrain reticular formation and cortex of mouse brain following various treatments. The results indicate that only glutamate among the 3 neurohumors is systematically altered relative to the experimental manipulations. Moreover, among the 4 brain areas examined, the data implicate only the periaqueductal central gray matter as a locus of morphine's antinociceptive action. Morphine also appears to produce a drug-specific effect in hypothalamus which, however, is not analgesia-related. There were no significant pain, stress or drug-related effects on the levels of glutamate in either the midbrain reticular formation or the cortex.

The neocortex receives a major cholinergic innervation from magnocellular neurones in the basal forebrain1–3. However, an ascending cholinergic reticular system has also been postulated to arise from acetylcholinesterase (AChE)-containing neurones in the midbrain and pontine tegmentum4–5. Lesions of this region decrease both AChE and choline acetyltransferase (ChAT) in various forebrain areas6,7, and recent immunohistochemical studies have identified a group of ChAT-containing cell bodies in the midbrain reticular formation and dorsolateral pontine tegmentum8,9. Here we have combined retrograde tracing with ChAT immunohistochemistry to demonstrate that this tegmental cholinergic cell group also directly innervates the cerebral cortex. Other immunohistochemical studies have indicated that the neuropeptide substance P is also present in certain cells in the laterodorsal tegmentum10, and these too appear to project to the forebrain11,12. We have therefore performed immunohistochemistry for both ChAT and substance P and have discovered that a subpopulation of the ascending cholinergic reticular neurones contains substance P. Thus, peptide–cholinergic coexistence, previously noted in peripheral neurones, also occurs in the brain.

Twenty cats were prepared surgically with electrodes for recording the EEG, Eye Movements and EMG and a push-pull cannula system in the midbrain reticular formation (MRF) allowing the extraction of perfusates during wakefulness or REM sleep. Proteins in the perfusates were analyzed by Isoelectric Focusing (IEF) polyacrylamide gels and Sodium Dodesyl Sulphate (SDS) slab gels. In addition analysis of glycoproteins was done by gas chromatography. In some cats the contribution of cerebrospinal fluid (CSF) proteins to perfusate proteins from brain tissue was studied by intraventricular injections of labelled leucine. The effect of sleep alterations on the protein cycle during sleep and wakefulness was also studied. The results of these experiments showed that most of the proteins in the perfusates are acidic, and that REM sleep perfusates contain 2 proteins M.W. 73.000 and 45.000 not present in awake perfusates, CSF or serum. It was also shown that CSF proteins do not appear to contribute to the proteins in perfusates, and that altering the sleep wake cycle, induces changes in the rhythm of protein release in perfusates. It is suggested that some relatively large polypeptides may participate in the regulation of REM sleep.

The modulatory inputs of the cholinergic neurons of the nucleus basalis have been investigated in midpontine transected and freely moving rats by measuring acetylcholine release from the cerebral cortex using the cortical cup technique. Acetylcholine release was found to be the same in both groups of rats indicating similar levels of activity of the cholinergic neurons ascending to the cortex. The electrical stimulation of the nucleus basalis was always followed by an increase in acetylcholine release. Conversely, in some experiments only the stimulation of the midbrain reticular formation enhanced acetylcholine output. The stimulation of the nucleus accumbens prevented the increase in acetylcholine release elicited by amphetamine. The dose-dependent increase in acetylcholine output following IP administration of amphetamine was also prevented by the 6-hydroxydopamine induced degeneration of the dopaminergic fibres. However injection of apomorphine in the nucleus basalis did not modify acetylcholine output. Direct injection of the GABAergic agonist muscimol resulted in a decrease in acetylcholine output which was prevented by picrotoxin. In conclusion, the cholinergic neurons ascending to the cortex can be inhibited by GABA receptors located in the nucleus basalis and stimulated indirectly by dopaminergic fibres.

The present study investigated the role of the midbrain reticular formation (MRF) in the expression of opposing locomotor asymmetries elicited from the medial and lateral substantia nigra pars compacta (SNC). It was found that unilateral MRF lesions produced ipsiversive circling that was potentiated by amphetamine. Lateral SNC lesions produced contraversive circling while medial SNC lesions caused ipsiversive circling. When SNC lesions were combined with MRF lesions animals circled ipsiversively as they did with MRF lesions alone regardless of whether the SNC lesion was in the medial or lateral part of the SNC. Taken together, the results are consistent with the notion that a striato-nigral-MRF system is an output path for circling derived from both the medial and lateral SNC.

A bilaterally induced mechanical lesion of the midbrain was highly effective in abolishing the hindlimb extensor (HLE) component of the maximal electroshock seizures (MES) in rats. Although these lesions produced damage to a variety of midbrain structures, correlations between different lesion placements and effects in the MES test provided evidence that damage to superior cerebellar peduncle (PCS) and/or reticular formation (RF) was responsible for inhibition of hindlimb extension. Moreover, discretely placed electrolytic lesions disrupting either the PCS or the RF were found to abolish the hindlimb extensor component of the MES test. These findings are consistent with the work of other investigators showing that total cerebellectomy abolishes the HLE component of MES and suggest that activity in the cerebellum and the midbrain reticular formation plays a major role in regulating the tonic phase of electroshock induced seizures.

The effect of azelastine, a new anti-allergic agent which possesses a variety of anti-allergic effects in addition to its H1-blocking action, on the central nervous system was studied by observing the changes in EEG and behavioral state in unanesthetized rats. Certain H1-receptor antagonists such as promethazine, diphenhydramine, and homochlorcyclizine induced the drowsy pattern in EEGs at doses less than 5mg/kg. The pattern is characterized by high voltage and slow waves and is not interrupted by auditory stimulation. At 5mg/kg both promethazine and diphenhydramine blocked the EEG arousal response induced by electrical stimulation of the midbrain reticular formation (0.5 msec, 4V, 100 Hz for 5 sec). Diphenhydramine also diminished the photic driving responses significantly. Even at 10mg/kg (iv), azelastine had little EEG effect and did not prevent the EEG arousal responses provoked by both auditory and reticular stimulations. Further, the photic driving response was not inhibited at all by the same dosage of azelastine.

Single unit activity was recorded extracellularly from the midbrain of rats during fighting behavior and during non-fighting control manipulations. Fighting behavior was elicited by footshock or startle stimuli or occurred spontaneously as a result of prior footshock presentations. Seven cells were found in the midbrain reticular formation and central gray which displayed maximum firing rates during fighting behavior. These cells also fired to a limited extent to some of the control manipulations, particularly contralateral vibrissae stimulation. These cells fired phasically during fighting behavior and their firing was correlated with either the approach or paw-strike of the opponent animal or to the response of the recording animal to a tactic of the opponent animal. However, no specific movement or sensory event reliably predicted the firing of these cells during fight sequences. Cells located in other midbrain areas, such as the deep tectum or the area of the red nucleus, also responded during fighting behavior. However, the discharge of these cells was correlated with specific body movements or sensory events. The activity during fighting was similar in rate and pattern to activity during control manipulations whenever similar movements or sensory stimulation were produced. Cells were also found which did not discharge during fighting behavior although they fired under a variety of other conditions.