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The effect of estradiol on opioid receptor density in the hypothalamus of female rats was examined by in vitro receptor autoradiography using [3H]naloxone as the ligand. Exposure of ovariectomized rats to estradiol for 48 h markedly increased the density of [3H]naloxone binding in both the ventral and dorsal premammillary nuclei but not in other regions of the hypothalamus or amygdala. Thus, estrogen selectively modulates opioid receptor binding in posterior hypothalamic regions involved in gonadotropin secretion and temperature regulation.

Diseases that affect the striatum produce movement disorders, for which rats have been a useful model. To determine the organization of functional, neural activity in the rat striatum related to motor activity, we used electrical stimulation of the motor cortex and [14C]deoxyglucose autoradiography. The stimulation produced movements of each of three body regions. Both the motor and somatosensory cortex were activated. Image analysis was used to objectively localize peak activation and to provide a map for further stereotaxic and localization studies. In the anterior striatum, in the dorsolateral sector, regions of peak activation were well separated for each body region: the hindlimb peak activation was dorsomedial, the forelimb ventrolateral and vibrissae medial. Also, the activation fields were larger in anterior than in posterior striatum. Furthermore, activation ipsilateral to movement was present and the peak localization was offset from peaks contralateral to movement. In addition, there were activation regions in lateral striatum where body region representations may overlap. This is the first demonstration of a global striatal somatotopy that separates the limbs and vibrissae in rats. The functional average revealed by the deoxyglucose autoradiography showed a predominant isotropic or rod-like representation of sensorimotor activity for the limbs in striatum during movement and confirms aspects of the anatomy known for the corticostriate system in primates: metabolism was 'patchy,' and extended throughout long anteroposterior domains in striatum. These extensive and patchy arrangements suggest integrative, combinational and/or associative networks.

The mature brain is less susceptible to seizures than the immature brain. We demonstrate that in the mature substantia nigra (SN) there are two topographically discrete GABAA-sensitive regions which differ in the amount of mRNA expression of the GABAA receptor alpha 1 subunit. These two regions mediate separate anticonvulsant and proconvulsant effects and use divergent projection networks. By contrast, in the immature SN there is no special topography of mRNA expression of the alpha 1 subunit and only the proconvulsant network is present. The decreased seizure susceptibility of the mature brain may be related to postnatal segregation of GABAA-sensitive networks.

Three techniques, namely, midbrain lesions, fluorescence histochemistry and brain cannulation, were used in combination to analyze catecholamine (CA) projections to the perifornical hypothalamus and their function in suppressing feeding behavior. The convergence of evidence indicates that the ventral adrenergic component of the central tegmental tract and dopaminergic projections from midbrain A8 and possibly A9 cell groups contain the crucial fibers which innervate the perifornical hypothalamus and mediate CA suppression of feeding behavior. The primary evidence for this conclusion is that ventral tegmental electrolytic or 6-OHDA lesions which damaged specifically these fibers invariably caused: (1) a marked reduction of CA varicosities in the perifornical area; (2) a strong reduction or loss of the anorectic response produced by perifornical injection of the presynaptically acting drugs amphetamine and mazindol; and (3) a potentiation of the anorectic response produced by perifornical injection of the CA receptor agonists dopamine and epinephrine. Lesions in the dorsal midbrain tegmentum, which left intact the ventral adrenergic and dopaminergic fibers but damaged the compact dorsal tegmental bundle, the dorsal fibers of the central tegmental tract and the medial and lateral tegmental CA radiations, had no apparent effect on the responsiveness of the perifornical hypothalamus to CA drug stimulation, as well as on the CA fluorescence in that region. Lesions in the area of the dopaminergic A10 cells and the midline tegmental CA radiations actually potentiated the effectiveness of the anorexigenic drugs in the perifornical hypothalamus.

Glucose utilization was measured in 5 regions of rat striatum within four anterior-posterior levels. Areas of minimal and maximal glucose utilization were identified. Density-window image analysis was used to quantify areas of minimal and maximal glucose utilization, which were also apparent upon close visual inspection. In a normal control group, there were substantial regional variations in striatal glucose utilization (e.g. dorsal vs ventral; dorsomedial vs dorsolateral), revealing a detailed pattern, previously unavailable, which served as a baseline to study the effect of systemic apomorphine. The highest levels of glucose utilization were in small islands 0.01-0.25 mm2, and in what appeared to be dense clusters of islands that formed larger zones. Apomorphine treatment decreased glucose utilization in dorsomedial regions, increased it in a ventromedial region, and did not change it in others. The findings emphasize the importance of regional analysis of striatum in functional and physiological studies, and provide a new baseline for analyses of striatal glucose utilization in studies of development and aging, drug effects, external stimuli, and rat models of movement disorders.

Local cerebral glucose utilization (LCGU), estimated by the quantitative autoradiographic 2-deoxyglucose technique, was studied in rats with bilateral 6-hydroxydopamine lesions of the locus coeruleus (LC) and in vehicle-injected controls. Unanesthetized animals were studied during exposure to stressful levels of white noise (95 dB) or in relative silence (50 dB). Results indicated that noise caused greater and more widespread increases in LCGU in animals with LC lesions than in vehicle-injected controls. Lesions alone had little or no effect in animals not subjected to noise. Analyses of variance revealed significant treatment interaction effects (intact/lesion x silence/noise) for 37 of 109 regions measured. The pattern of results suggests that the LC acts during stress to limit unnecessary cerebral activity that might interfere with efficient sensory processing and/or the organization of appropriate behavioral responses. In this respect LC function may be similar to those actions of the peripheral sympathetic nervous system that suppress vegetative functions during stress to allow for the performance of coping responses.

Three techniques, namely, midbrain lesions, fluorescence histochemistry, and brain cannulation, were used in combination to analyze noradrenergic projections to the paraventricular nucleus of the hypothalamus (PVN) and their function in stimulating feeding behavior. The convergence of evidence indicates that the dorsal component of the central tegmental tract (CTT), which ascends through the dorsal pons and then projects through the medial tegmental radiations (TR) into the ventral tegmentum just dorsal to the media lemniscus, contains the crucial noradrenergic axons which innervate the PVN and mediate noradrenergic stimulation of feeding behavior. The primary evidence for this conclusion is that dorsal tegmental electrolytic or 6-OHDA lesions which damaged specifically these fibers invariably caused: (1) a reduction of catecholamine varicosities within the PVN (most notably, fine and moderate-size, rounded varicosities within the parvocellular area); (2) a strong reduction or loss of the feeding response elicited by PVN injection of the presynaptically-acting drugs tranylcypromine and desipramine; and (3) a potentiation of the same response produced by injected norepinephrine. These pharmacological and neurochemical changes in the PVN were reduced in magnitude if the dorsal CTT and medial TR fibers received only partial damage, and these changes did not occur at all if the lesion fell immediately dorsal to these fibers without damaging them. Specific lesions in the ventral tegmentum, which also failed to damage the dorsal CTT and TR axons but instead damaged the ventral component of the CTT, not only failed to disrupt the action of the antidepressant agents but actually potentiated their effectiveness in the PVN. Ventromedial lesions, however, which severed the rostroventral extension of the dorsal CTT and medial TR fibers, had the same behavioral consequences as had the dorsal lesions which damaged this projection at a more dorsocaudal level. Finally, damage to other catecholamine projections had little effect on PVN function in stimulating eating.

Rats which had exhibited contralateral rotation following unilateral injection of dopamine (DA) through a striatal cannula were given 0.5 - 50 micrograms DA intrastriatally and then were injected with [14C]deoxyglucose peripherally to measure glucose utilization in the striatum and its projection nuclei. Quantitative autoradiographic techniques were used to measure glucose utilization. Brain areas which showed L-R asymmetries and changes in glucose utilization different from vehicle-injected animals were: the substantia nigra (pars compacta and pars reticulata), the subthalamic n., entopeduncular n., lateral habenula, and deep layers of the superior colliculus. The globus pallidus was affected also, but only in one group for which the injected DA may have spread and affected it directly. Each of these areas receives projections from the striatum or is one additional synapse away. Intrastriatal injections of norepinephrine, isoproterenol, and procaine did not produce changes in glucose utilization in the striatal projection nuclei. The results support the existence of a DA-sensitive strionigral system to both the reticulata and compacta regions of the nigra, and suggest that this activity is paralleled by a strio-subthalamic and strio-entopeduncular-habenular system. The onset of changes in glucose utilization in the entopeduncular-habenular system was later than in the strio-subthalamic and strionigral systems and correlated with the onset of rotation. However, data from 4 animals which did not rotate suggest that each of these systems is necessary but not sufficient for rotation. It is concluded that DA receptors in the striatum play a significant role in the effects of peripherally administered DA agonists on other nuclei, even though most of these other nuclei also have their own DA receptors.

This study was designed to assess effects of insulin-induced hypoglycemia on plasma and cerebrospinal fluid (CSF) levels of immunoreactive (ir) beta-endorphins, adrenocorticotropin (ACTH), cortisol, norepinephrine, insulin, and glucose in the conscious, overnight fasted dog. Dogs received either an intravenous infusion of saline or insulin (5 mU/kg/min) for 3 h. Infusion of saline alone in conjunction with acute sampling of CSF caused no measurable perturbations of glucose homeostasis. Insulin infusion caused a 60% drop in both plasma and CSF glucose. Plasma levels of ir-beta-endorphins, ACTH and cortisol rose markedly. CSF levels of ir-beta-endorphins and ACTH also increased. While the magnitude of the increase was smaller than that in the plasma, it was greater than would be expected if crossover of the peptides from the plasma were the sole source of the increase. Hypoglycemia also induced elevations in CSF cortisol and insulin. In addition, there was a 45% decrease in CSF norepinephrine in spite of large elevations of norepinephrine in the plasma. We conclude that hypoglycemia is associated with marked changes in central as well as peripheral levels of neuroendocrine factors. The importance of these changes in mediating acute and long-term responses to hypoglycemia remains to be established.