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The aim of this study was to examine the effects of asphyxia-reventilation and hyperoxia on the cerebral blood perfusion and prostanoid production of the brain arteries and microvessels in piglets. After 10 min of asphyxia, animals were ventilated with room air, or with 100% O2. Following 4 hours of recovery, the brains were perfused, cerebral arteries were removed and microvessels were isolated from the cortex. The microvessels and the arteries were incubated with 1-14C-arachidonic acid, and the 1-14C-prostanoids were then separated by means of overpressure thin-layer chromatography and were quantitatively determined. Under control conditions, the synthesis of dilatory prostanoids dominated the arachidonate cascade both in the microvessels and in the arteries. Asphyxia and reventilation with room air did not modify the prostanoid production. O2 ventilation greatly affected the prostanoid synthesis of the microvessels, with an enhancement of PGD2 up to 247 +/- 27%. In the arteries, the production of PGI2 and of PGE2 was elevated to 272 +/- 15% and to 148 +/- 13%, respectively. These findings indicate that O2 ventilation after asphyxia substantially increases the extent of prostanoid synthesis in the cerebral blood vessels.

The role of substance P (SP) in neurogenic inflammation is well known. Through neurokinin receptors, SP activates cells, including the arachidonate cascade of platelets. Our in vitro experiments were carried out to determine the effect of SP on the arachidonate cascade of rat platelets. The platelets were labelled with 14C-arachidonic acid, and the 14C-eicosanoids were then separated by means of overpressure thin-layer chromatography or high-performance liquid chromatography and were quantitatively determined. SP (10(-9) and 10(-8)) mol/L significantly increased the rate of the arachidonate cascade. The lipoxygenase pathway of platelets was stimulated by SP, which can result in the activation of protein kinase C mediated intracellular events. The cyclooxygenase system was inhibited by 10(-12) mol/L, and stimulated by 10(-9) mol/L SP. In our experiments SP in the physiological range of plasma concentration (10(-12) mol/L) decreased the synthesis of vasoconstrictor arachidonate metabolites (TxA2 and PGF2 alpha). These data suggest that in physiologic conditions the arachidonate cascade of platelets may play role in the vasodilator effect of SP. The formation of thromboxane in rat platelets was stimulated by higher concentration of SP (10(-9) mol/L), and therefore the SP-induced cytotoxicity against parasites might be mediated by the stimulation of thromboxane A2 synthesis.

Satiated rats received intracerebroventricular (icv.) injections of several doses of neuropeptide Y (NPY) and the food intake was measured in the following 4 h. The peptide exerted a dose-dependent biphasic effect; the 100 dose significantly suppressed the food intake, but doses of 1 microgram and 5 micrograms stimulated feeding. After the injection of 2 microliters NPY-antiserum (icv., 1:50 dilution), the cumulative food intake decreased significantly in the first 24 h. From the drugs tested the alpha-1-antagonist prazosine (4 micrograms icv.) and the opiate antagonist naloxone (NX, 0.5 micrograms, icv.) selectively inhibited the feeding-stimulatory effect a high icv. dose of NPY. The alpha-2-antagonist yohimbine (4 micrograms icv.) and the non-selective beta-antagonist propranolol (5 micrograms icv.) did not influence either effect of NPY on feeding. The results suggest the involvement of alpha-1-adrenergic and opiate receptors in the food intake-stimulatory effect of a large icv. dose of NPY. The food intake-inhibitory effect of a low icv. peptide dose was not selectively antagonized by the receptor blocking agents used.

5-hydroxytryptamine at a concentration of 0.04 microgram/ml was able to block the ACTH release caused by hypothalamic tissue (CRF) while it was ineffective when a hypothalamic extract containing CRF was used. 5-hydroxytryptophan added to rat adrenal tissue caused a dose-dependent increase in corticosterone production. In a dose of 0.04 microgram/ml, 0.4 microgram/ml and 4.0 microgram/ml, 5-hydroxytryptophan was able to inhibit the ACTH release caused by hypothalamic tissue in vitro. However 0.04 microgram/ml was ineffective on the increase in ACTH secretion elicited by hypothalamic extract CRF. The data suggest that the inhibitory action of 5-hydroxytryptophan and 5-hydroxytryptamine is exerted at the hypothalamic level by inhibiting the release and/or synthesis of the corticotrophic releasing factor.

Somatostatin administered intracerebroventricularly inhibited the extinction of active avoidance behaviour. The dopamine receptor blocking agent haloperidol, the alpha 1-receptor blocker phenoxybenzamine and the muscarinic anticholinergic agent atropine inhibited the behavioural effect of the peptide. Furthermore, somatostatin increased the locomotor activity of the animals. Neither of these drugs influenced the effect of the peptide exerted on locomotor activity. The peptide was ineffective on other parameters of the open-field test while phenoxybenzamine decreased the defecation rate of the animals and this effect was not influenced by somatostatin. The results suggest that the catecholaminergic and the cholinergic system play an important role in the inhibition of extinction produced by somatostatin but these mechanisms to not have a role in the locomotor activity induced by the peptide.

The effect of dipeptides was studied on naloxone-precipitated morphine withdrawal in the mouse. In accordance with previous data, s.c. treatment with Z-prolyl-D-leucine delayed the onset of withdrawal jumpings . Replacement of L-proline by L-glutamate or L-pyroglutamate resulted in dipeptides which were more potent in morphine withdrawal than was Z-prolyl-D-leucine.

Two doses (0.3 and 3 ng peptide/animal) of oxytocin (OXT) and lysine-8-vasopressin (LVP) were earlier found to inhibit the development of tolerance to the hypothermic effect of ethanol in mice upon icv. administration. In the present paper the possible central monoaminergic correlates of the behavioral data were investigated. In tolerant animals the steady-state level of noradrenaline (NA) was increased in the hypothalamus, as was that of dopamine (DA) in the medulla oblongata; the serotonin (5-HT) and DA levels were decreased in the striatum as compared to those in the non-tolerant control. In the peptide-pretreated animals the NA level was increased in the hypothalamus, the DA level in the striatum, and the 5-HT level in the hippocampus and striatum. Opposite changes were observed in the steady-state levels of the monoamines in the hippocampus and striatum as compared to those in the tolerant controls. The data suggest that the central monoamines may be involved in mediating the actions of neurohypophyseal peptides on ethanol tolerance.

The effect of different doses of intracerebro-ventricularly administered cholecystokinin octapeptide sulphate ester (CCK-8-SE) was studied on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents in the hypothalamus, mesencephalon, amygdala, septum and striatum, 10, 20 and 60 min following administration. The DA and NE content increased and the 5-HT content decreased in the hypothalamus and mesencephalon. A biphasic action was observed in the amygdala of DA, NE and 5-HT depending upon the time and doses used. Similar action was seen on DA and NE in the septum. In the striatum, the DA and 5-HT content decreased while the NE level first increased and then decreased. The data indicate that the CCK-8-SE is able to modify the activity of DA, NE and 5-HT in different brain regions in a time and dose-dependent manner, with a local specific action.

Increased vascular permeability was induced by prostaglandin E2 (PGE1), arachidonic acid and compound 48/80 in male rats. Natural ACTH in a dose-dependent manner inhibited Evans blue exudation elicited by arachidonic acid or compound 48/80, however, it was ineffective against PGE1. ACTH4--10 (d-Phe7 and 1-Phe7) injected together with the prophlogistic agents depressed the arachidonic acid and compound 48/80 induced vascular reaction. Indomethacin pretreatment inhibited the effect of arachidonic acid on vascular permeability suggesting that arachidonic acid evoked its vascular activity by means of affecting the endogenous synthesis of prostaglandins and, on the other hand, the prostaglandin system played a role in the vascular permeability inducing effect of compound 48/80. ACTH4--10 peptide fragments free of steroidogenic action and natural ACTH inhibited locally the in vivo formation of PGS from arachidonic acid in the rat skin, resulting in a nonspecific decrease of local inflammation.

The effect of somatostatin and its two tetrapeptide fragments was investigated on turning activity induced by unilateral substantia nigra lesion in rats. Somatostatin in a dose of 0.6 nM had no action on the turning behavior, while a dose of 6 nM increased slightly while a dose of 12 nM significantly the contralateral turning. Cys-Lys-Asn-Phe and Phe-Trp-Lys-Thr had no action in low or high doses on the turning activity of the animals. The results suggest that somatostatin has a direct postsynaptic dopamine receptor stimulating effect. It seems that for dopamine receptor stimulating action the complete somatostatin molecule is needed.

The action of cyclic and linear somatostatin on active avoidance and open-field behaviour was investigated in rats. Both peptides inhibited the extinction of the avoidance behaviour and slightly but not significantly increased the intertrial activity (ITR). Both peptides increased ambulation and rearing activity in a dose related fashion, while the grooming and defecation rates were not changed. Since both peptides are capable of increasing the locomotor performance this action might contribute to the effect exerted on the extinction of active avoidance behaviour.

Oxytocin (500 mu u) and vasopressin (50 mu u) were injected into the lateral ventricle and its effect on hypothalamic self-stimulation has been studied. Oxytocin increased, while vasopressin decreased the self-stimulation rate tested 10-20 min following application. The hypothalamic and mesencephalic serotonin content decreased slightly while plasma corticosterone content did not change 20 min after oxytocin and vasopressin administration compared to the injected control animals. The data suggest that vasopressin and oxytocin have an opposite effect on self-stimulation and this action is not mediated through the brain serotoninergic or pituitary-adrenocortical axis.

The effects of 5 microgram prostaglandin (PG) A1, E1, E2 and F2 alpha injected intracerebroventricularly (i.c.v.) into conscious male rats were studied on the catecholamine contents of certain brain areas at different times after administration. PGE2 led to increased dopamine (DA) contents in the hypothalamus 10, 20 and 60 min, and in the septal region 20, 60 and 90 min following injection. PGE1 raised DA levels in the hypothalamus 20 min, and in the septum 20 and 60 min after i.c.v. administration. PGA1 and PGF2 alpha proved to be ineffective as regards the DA contents, while none of the PGs studied altered the noradrenaline (NA) contents of different brain areas. Disappearance of DA was significantly enhanced in the hypothalamus and in the septum, while NA disappearance rate was increased only in the hypothalamus after PGE1 and PGE2 i.c.v. injection in alpha-methyl-p-tyrosine treated rats.

The effects of lysine8-vasopressin (LVP) on the open-field activity and passive avoidance behaviour in rats were studied following intracerebroventricular (i.c.v.) and intracisternal (c.m.) administration. Following i.c.v. administration, LVP caused a long-lasting facilitation of the passive avoidance behaviour and did not influence open-field activity. When injected into the cisterna magna, on the other hand, the same amount of LVP was without effect on the passive avoidance behaviour, while decreasing open-field activity. It is concluded that the site of injection in the cerebrospinal space might be of importance in determining the behavioural effects of neuropeptides.

The effects of different doses of lysine vasopressin (LVP) and oxytocin (OXT) were studied on the six-day acquisition or extinction of a food-reinforced classical conditioning reflex (conditional stimulus: light) when intraperitoneal (ip.) injections were carried out 20 min prior to the behavioural sessions. The highest (600 mU/kg) dose of LVP inhibited acquisition, and all LVP doses tested (150, 300 and 600 mU/kg) facilitated the extinction of conditioned behaviour. These same mU doses of OXT did not significantly affect the food-reinforced conditioning, although a consequent tendency towards increased performance (the opposite action to vasopressin) was observed. When 2.5 or 25 micrograms/kg doses of desglycinamide-arginine-vasopressin (DGAVP), a 500 micrograms/kg dose of prolyl-leucyl-glycinamide (PLG) or a 1200 mU/kg dose of OXT was injected during the extinction sessions, 2.5 micrograms/kg DGAVP and 1200 mU/kg OXT significantly facilitated extinction; the other treatments were without effect. LVP in a dose of 300 or 600 mU/kg and OXT in a dose of 300, 600 or 1200 mU/kg did not influence the food intake of 22 h food-deprived rats in a nonconditional situation. The present results indicate that the effects of LVP and OXT on memory display reinforcement-dependent characteristics, and are thus indirect or non-specific in nature.

In the present study the dose-related effects of linear and cyclic somatostatin were compared on the self-stimulation rate of rats. Twenty micrograms of linear somatostatin administered intracerebroventricularly (icv.) markedly decreased the self-stimulation rate, while 5 micrograms and 10 micrograms was ineffective. Cyclic somatostatin in a dose of 1 microgram caused a transitory but not significant increase in the self-stimulation rate, which later returned to the control level. Five micrograms and 10 micrograms of the peptide decreased the self-stimulation rate. These results indicate that the cyclic somatostatin is more effective in inhibiting the self-stimulation rate than the linear one.

Treatment or implantation of oestrone, oestradiol or progesterone on the third day postpartum into the ventromedial-arcuate region of the hypothalamus produced a complex pattern of changes in established maternal behaviour in rats. Progesterone implanted into the ventromedial-arcuate region of the hypothalamus increased the time spent nursing. In contrast, it was shortened by oestradiol given subcutaneously or implanted hypothalamically or extrahypothalamically, or by oestrone implanted into the hypothalamus. Oestradiol by an route used oestrone implanted into the hypothalamus caused marked reduction of pup weight and retrieval frequency. Progesterone had no such effect. Maternal care involving retrieval, sniffing, licking and nursing, expressed in seconds care, declined after hypothalamic and systemic oestradiol treatment. However, oestrone implanted into the hypothalamus increased seconds of care on days 9 and 10. Progesterone did not affect this function.

The effects of intracerebroventricular administration of cholecystokinin (CCK) antiserum )specific for COOH-terminal four amino acids) of CCK were tested in three dilutions on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) contents of the hypothalamus, amygdala, septum, striatum and cerebral cortex in rats 24 h following application. CCK antiserum decreased the DA and NE contents in the hypothalamus, mesencephalon, amygdala and septum, while it increased the DA content and decreased the NE content of the striatum. It had a slight effect on the 5-HT contents of the amygdala, septum and striatum.

Fifteen min after ether stress, the 5-hydroxytryptamine (5-HT) content of the rat hypothalamus decreased, while after electric shock no decline was noted in the mesencephalon and the hypothalamus. At 30 min an increase occurred in the mesencephalon and amygdala and at 60 min in the hypothalamus after both stressors. Fifteen min after electric shock the 5-hydroxyindoleacetic acid (5-HIAA) content was increased in the amygdala, while after both stressors in the mesencephalon and hypothalamus 30 min and after ether stress in the amygdala. In the hippocampus and the septum the 5-HT or 5-HIIA content was unaffected by either type of stress. 5-HT turnover decreased between 10 and 20 min after ether stress in the hypothalamus and after electric shock in the mesencephalon and hypothalamus. Between 50 and 60 min after electric shock, 5-HT turnover increased in the mesencephalon. Other brain areas showed no significant difference from the control 5-HT value. 3H-5-HT uptake decreased in the mesencephalon and hypothalamus 20 min after ether stress, but returned to normal after 60 min. The plasma corticosterone level was highest at 30 min after both stressors and returned to normal 90 min after stress. Therefore, the stress-induced decrease of serotoninergic activity in certain limbic brain structures, especially in the hypothalamus, suggests an inverse relationship with pituitary-adrenal activity. This finding would further support the concept that the serotoninergic system plays an inhibitory role in pituitary-adrenal function.

The effect of electroconvulsive therapy used in psychiatry was investigated in rats. Electroconvulsion significantly increased the plasma prolactin, and decreased the hypothalamic dopamine content. The adrenal response (increase in plasma corticosterone) did not differ from the control groups. The results indicate that the prolactin response elicited by electroconvulsion is due to monoaminergic influence and not to the stress reaction.

The effect of prostaglandins (PG) A1, E1, E2 and F2 alpha in the concentration range of 10(-7)--10(-4) M were studied in vitro on a rat hypothalamic tissue, collagenase-digested isolated anterior pituitary cell and Leydig cell suspension system by measuring the testosterone production of incubated Leydig cells. PGs did not change the testosterone production and the hCG sensitivity of the Leydig cells, nor the LH secretion and the LHRH sensitivity of the anterior pituitary cells. PGE2 at concentrations of 10(-6), 10(-5) and 10(-4) M significantly increased the hypothalamic tissue-induced pituitary-testicular activation, and this stimulatory effect of PGE2 was dose dependent. PGA1, PGE1 and PGF2 alpha did not alter hypothalamic LHRH release measured in vitro. The results suggest that PGE2 has a direct stimulatory effect on hypothalamic LHRH release.

Earlier it was found that oxytocin (OXT) treatment inhibited the development of tolerance to ethanol. In the present study the possibility was investigated whether the effect of OXT on ethanol tolerance was related to peptide fragments derived from the C-terminal part of the molecule. The actions of different doses of the C-terminal tripeptide (prolyl-leucyl-glycinamide, PLG) and of a synthetic dipeptide derivative (Z-prolyl-D-leucine, Z-Pro-D-Leu) on the development of tolerance to the hypothermic effect of ethanol in CFLP mice were therefore investigated. Peptide treatment did not affect body temperature in ethanol-naive animals. The acute effects (hypothermia, sleeping time) of a single ethanol injection were also unaffected by these peptides. In contrast, both PLG and Z-Pro-D-Leu inhibited the development of tolerance to the hypothermic effect of ethanol. Accordingly, it might be speculated that a sequence active in affecting ethanol tolerance is located in the C-terminal part of the OXT molecule.

Prolyl-leucyl-glycinamide (PLG) and its substituted and protected analogues were tested on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain areas. The tripeptides were structurally modified at the N-terminal proline residue either by protection with benzoxycarbonyl (Z group) or by tertiary butyroxycarbonyl (BOC), or by substitution with homoproline (HPRO). C-terminal modification was performed by substitution of the amino group of glycine (GLY-NH2) by methylester (GLY-OMe). The parent molecule (PLG) increased the 5-HT content in the striatum and the NA and DA levels in the dorsal hippocampus. N-terminal protection by Z-group resulted in a loss of these effects. Striatal effects re-appeared if a methylester group was introduced in the C-terminal glycine. Substitution of the N-terminal with HPRO or that of the C-terminal amine group by OMe resulted in a tendency to increase the 5-HT level in the hypothalamus.

The effects of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and unsulfated cholecystokinin (CCK-8-NS) were studied following intraventricular administration on active avoidance and conditioned feeding behaviour of rats. In the CCK-8-NS and CCK-8-SE treated animals the acquisition of active avoidance and conditioned feeding behaviour were considerably impaired compared to the control; furthermore, these peptides caused a facilitated extinction of active avoidance and conditioned feeding behaviour. The data suggest that cholecystokinin octapeptide is capable of modifying the fear and hunger motivated behaviours of rats.

The effects of different doses of human pancreatic polypeptide (HPP) injected into the third ventricle was studied on plasma follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (Prl) and somatotropin (GH) in freely moving ovariectomized rats. Two hundred ng of HPP produced a significant decrease in plasma LH at 15, 30, and 60 min following microinjection. The LH-lowering effect of 400 and 800 ng of HPP developed at 5 min and persisted throughout the experiment. The strongest inhibition was observed at 15 and 30 min. No change in plasma FSH was detected at any time during the experimental period. Two hundred and 400 ng of HPP failed to influence the plasma Prl, while 800 ng resulted in a moderate but significant decrease in plasma Prl levels at 15 and 30 min following injection. Intraventricular microinjection of 400 ng of HPP decreased the GH level at 15 min and 800 ng caused a more pronounced decrease which was significant at 15, 30, and 60 min after the injection. The study suggested that HPP, either from the periphery if it can pass the blood brain barriers or produced in the brain, can influence pituitary function.

Hypothalamic PGF2 alpha content was determined by radioimmunoassay in rats. The male animals had significantly higher PGF/2 alpha level than the females. The hypothalamic PGF2alpha content increased following orchidectomy (GDX), while ovariectomy alone or combined with oestrone (100 microgram/kg or 1mg/kg i.m.) resulted in a significant i.m.) alone was ineffective. Testosterone (1 or 5 mg/kg i.m.) in GDX animals restored the hypothalamic PGF2 alpha content to the control level. The synthesis and breakdown of prostaglandins were also studied in the microsomal and cytosol fraction of brain homogenate. The PGD2 was the main product of the arachidonate cascade in rat brain microsomes. OVX increased the formation of PGD2 and diminished the biosynthesis of PGF2 alpha. Oestrone administration to OVX rats enhanced the formation of PGF2 alpha. Progesterone injection decreased the biosynthesis of PGF2 alpha and PGD2 alpha and PGD2 in OVX animals. Combined administration of progesterone and oestrone to OVX rats failed to restore the PGF2 alpha synthesis. In orchidectomized animals the arachidonate cascade was found to be depressed, further the synthesis of prostaglandins was normalized after testosterone substitution. The inactivation of 3H-PGF2 alpha by rat brain cytosol fraction was negligible.

The review article summarizes the results obtained in the author's laboratory during the last few years concerning the action of number of neurohormones such as ACTH, vasopressin, oxytocin, TRH and TRH analogues, human chorionic gonadotropin (HCG) LH-RH, gastrin and gastrin C-terminal fragments and cholecystokinin octapeptide on certain behavioural reactions and brain transmitters. The results obtained suggests that in some of the behavioural reactions elicited by these peptide hormones are brought about by modulatory action of these peptide on brain transmitters. These neurohormones, including gastrointestinal peptide hormones have a time dependent, locus and transmitter specific action on the brain function.

The effect of modified and substituted analogues of prolyl-leucyl-glycinamide (PLG, MIF-I) was investigated on the steady-state level of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in various brain regions. Proline was replaced by D- or L-pipecolic acid (D- or L-Pip), which analogues in turn were protected by benzoxy-carbonyl (Z) group. Substitution by D- or L-pipecolic acid caused opposite changes in the DA level of the dorsal hippocampus. These effects were absent it the N-terminal of either analogues was protected by Z-group. Following the above mentioned N-terminal modification, the amino group of the C-terminal glycine was also substituted by methyl-esther (Gly-OMe), Z-D-Pip-Leu-Gly-OMe decreased the mesencephalic DA level, while Z-L-Pip-Leu-Gly-OMe increased the 5-HT content of the mesencephalon and striatum. In general, N-terminal substitution by D-pipecolic acid decreased, whereas that by L-pipecolic acid increased the monoamine level in the brain.

The dose-related effects of cysteamine treatment on hypothalamic and striatal neurotransmission were investigated. Cysteamine pretreatment with a dose of 150 mg/kg slightly increased the dopamine, and markedly decreased the noradrenaline, content of the hypothalamus in a dose-related manner. The serotonin levels of the hypothalamus and striatum were not affected. Cysteamine pretreatment with a higher dose (300 mg/kg sc) slightly increased the uptake of noradrenaline into hypothalamic slices. The drug did not influence dopamine and serotonin uptake into hypothalamus and striatal slices. These results suggest that cysteamine decreases rather selectively the noradrenaline content of the hypothalamus.

A modification of previously published fluorimetric methods for brain noradrenaline (NA), dopamine (DA), and serotonin (5-HT) assay is presented in this paper. The modification improved the sensitivity to 5-HT and resulted in a less time-consuming and less expensive method for noradrenaline and dopamine determination. The assay can be used for simultaneous estimation of NA, DA and 5-HT as well as for turnover studies, utilizing catecholamine synthesis inhibition or monoaminoxidase inhibition.

The effects of intracerebroventricular administration of different doses of cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated cholecystokinin octapeptide (CCK-8-NS) were tested on the latency of passive avoidance behaviour in rats. Treatments were carried out prior to learning trial, immediately after electroshock and prior to testing 24 h retention. Both CCK-8-NS and CCK-8-SE enhanced the latency of passive avoidance after all forms of treatment while showing different dose-response patterns depending on time of administration. These data indicate that CCK-8-SE and CCK-8-NS might play a role in the regulation of memory consolidation and retrieval.

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) was studied on dopamine, norepinephrine and serotonin turnover in the hypothalamus, mesencephalon, amygdala, septum, hippocampus, cortex and cerebellum following intracerebroventricular administration. Dopamine and norepinephrine turnover, measured by alpha-methyl-paratyrosine inhibition of catecholamine synthesis, increased in the cerebellum and the norepinephrine turnover in the hypothalamus. Serotonin turnover, measured by serotonin accumulation induced by the MAO inhibitor pargyline, decreased in the mesencephalon. There was no change in catecholamine or serotonin turnover in the amygdala, septum, hippocampus and cortex. The data suggested a highly selective action of glutaurine on brain transmitters in certain brain areas, especially in the cerebellum.

H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH after intracerebroventricular (icv.) administration inhibited the extinction of active avoidance behaviour for a short period. The dopamine receptor blocker haloperidol completely blocked this effect of the heptapeptide, while the muscarinic anticholinergic agent atropine only partly inhibited it. The alpha 1-receptor blocker phenoxybenzamine and the beta-receptor blocker propranolol did not significantly influence the extinction inhibition induced by the peptide. These results suggest that the dopaminergic and, in part the cholinergic system, play important roles in this behavioural action of H-Phe-Ile-Tyr-Ser-Tyr-Lys-OH.

The effects of intracerebroventricular administration of two different cholecystokinin antisera were tested on acquisition and extinction of active avoidance behaviour as well as on acquisition, maintenance and extinction of conditioned feeding behaviour of rats. Both antisera delayed the extinction of active avoidance and conditioned feeding response, while they were ineffective on acquisition and maintenance. These data suggest that the endogenous CCK of the brain might be a physiological modulator of extinction processes.

Effects of intraperitoneal administration of cholecystokinin (CCK)-related peptides were studied on retention of single-trial learning passive avoidance behaviour. The COOH-terminal octapeptide of CCK (CCK-1-8-SE), the unsulfated octapeptide (CCK-1-8-NS), as well as the COOH-terminal tetrapeptide of CCK (CCK-5-8), administered immediately after the learning trial, facilitated passive avoidance behaviour. The data indicate that these peptides may influence memory consolidation processes.

The effects of peripherally administered cholecystokinin octapeptide sulphate ester and its unsulphated form on the active avoidance behaviour of rats were studied. The acquisition of avoidance behaviour was impaired, while extinction was facilitated, following cholecystokinin octapeptide sulphate ester or unsulphated cholecystokinin octapeptide treatment. These peptides had no action on open-field activity. It is concluded that peripherally administered cholecystokinin octapeptide influences acquisition and extinction of active avoidance behaviour and this effect is unrelated to general motor activity of the animals.