Search

The GPR103 receptor is a G protein-coupled receptor, which plays a role in several physiological functions. However, the role of the GPR103 receptor in anxiety has not been clarified. The first aim of our study was to elucidate the involvement of the GPR103 receptor in anxious behavior. Mice were treated with peptide P550, which is the mouse homolog of neuropeptide 26RFa and has similar activity for the GPR103 receptor as neuropeptide 26RFa. The anxious behavior was investigated using an elevated plus-maze paradigm. The second aim of our study was to investigate the underlying neurotransmissions. Accordingly, mice were pretreated with a nonselective muscarinic acetylcholine receptor antagonist, atropine, a γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a D2, D3, D4 dopamine receptor antagonist, haloperidol, a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a nonselective β-adrenergic receptor antagonist, propranolol. Our results demonstrated that peptide P550 reduces anxious behavior in elevated plus maze test in mice. Our study shows also that GABAA-ergic, α- and β-adrenergic transmissions are all involved in this action, whereas 5-HT1 and 5-HT2 serotonergic, muscarinic cholinergic and D2, D3, D4 dopaminergic mechanisms may not be implicated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The extensive projection of orexigenic neurons and the diffuse expression of orexin receptors suggest that endogenous orexins are involved in several physiological functions of the central nervous system, including learning and memory. Our previous study demonstrated that orexin A improves learning, consolidation and retrieval processes, which involves α- and β-adrenergic, cholinergic, dopaminergic, GABA-A-ergic, opiate and nitrergic neurotransmissions. However, we have little evidence about the action of orexin B on memory processes and the underlying neuromodulation. Therefore, the aim of the present study was to investigate the action of orexin B on passive avoidance learning and the involvement of neurotransmitters in this action in rats. Accordingly, rats were pretreated with the selective orexin 2 receptor (OX2R) antagonist, EMPA; the γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, the bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; the nonselective opioid receptor antagonist, naloxone; the non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; the nonselective α-adrenergic receptor antagonist, phenoxybenzamine and the β-adrenergic receptor antagonist, propranolol. Our results demonstrate that orexin B can improve learning, consolidation of memory and retrieval. EMPA reversed completely the action of orexin B on memory consolidation. Bicuculline blocked fully; naloxone, nitro-l-arginine, phenoxybenzamine and propranolol attenuated the orexin B-induced memory consolidation, whereas haloperidol was ineffective. These data suggest that orexin B improves memory functions through OX2R and GABA-ergic, opiate, nitrergic, α- and β-adrenergic neurotransmissions are also involved in this action., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Orexins are hypothalamic neuropeptides, which are involved in several physiological functions of the central nervous system, including anxiety and stress. Several studies provide biochemical and behavioral evidence about the anxiogenic action of orexin A. However, we have little evidence about the underlying neuromodulation. Therefore, the aim of the present study was to investigate the involvement of neurotransmitters in the orexin A-induced anxiety-like behavior in elevated plus maze (EPM) test in mice. Accordingly, mice were pretreated with a non-selective muscarinic cholinergic antagonist, atropine; a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist, bicuculline; a D2, D3, D4 dopamine receptor antagonist, haloperidol; a non-specific nitric oxide synthase (NOS) inhibitor, nitro-l-arginine; a nonselective α-adrenergic receptor antagonist, phenoxybenzamine and a β-adrenergic receptor antagonist, propranolol 30min prior to the intracerebroventricular administration of orexin A. The EPM test started 30min after the i.c.v. injection of the neuropeptide. Our results show that orexin A decreases significantly the time spent in the arms (open/open+closed) and this action is reversed by bicuculline, phenoxybenzamine and propranolol, but not by atropine, haloperidol or nitro-l-arginine. Our results provide evidence for the first time that the orexin A-induced anxiety-like behavior is mediated through GABA-A-ergic, α- and β-adrenergic neurotransmissions, whereas muscarinic cholinergic, dopaminergic and nitrergic neurotransmissions may not be implicated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Neuromedin U (NmU), first was isolated from the porcine spinal cord, has subsequently been demonstrated in a number of species, in which it is present in the periphery and also the brain. Two receptors have been identified: NmU1R is mainly present in peripheral tissues, and Nmu2R in the central nervous system. NmU, a potent endogenous anorectic, serves as a catabolic signaling molecule in the brain; it inhibits food uptake, increases locomotion, activates stress mechanism, having cardiovasscular effects and, causes hyperthermia. The mechanism of this hyperthermia is unknown. In the present experiments, the effects of NmU on the colon temperature following i.c.v administration were studied in rats. For an investigation of the possible role of receptors in mediating hyperthermia, the animals were treated simultaneously with CRF 9-41 and antalarmin, a CRH1 receptor inhibitors, astressin 2B, a CRH2 receptor antagonist, haloperidol a dopamine receptor antagonist, atropine a muscarinic cholinergic receptor antagonist, noraminophenazone a cyclooxygenase inhibitor or isatin, a prostaglandin receptor antagonist. NmU increased the colon temperature, maximal action being observed at 2-3h. CRF 9-41, antalarmin, astressin 2B haloperidol, atropine, noraminophenazone and isatin prevented the NmU-induced increase in colon temperature. The results demonstrated that, when injected into the lateral brain ventricle NmU increased the body temperature, mediated by CRHR1 and CRHR2, dopamine and muscarinic cholinergic receptors. The final pathway involves prostaglandin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Neuromedin U (NmU) is a widely distributed and multifunctional peptide in the central nervous system and the peripheral tissues. Little is know about the mechanisms of NmU on brain functions. The rodent isoform of the NmU, NmU-23, has been shown to have anxiolytic effects involved in the β-adrenergic and cholinergic nervous systems in elevated plus maze test. NmU-23 was tested for antidepressant-like effects in modified forced swimming test (FST) in mice and furthermore, the involvement of the adrenergic, serotonergic, cholinergic, dopaminergic or gaba-ergic receptors in the antidepressant-like effect of NmU-23 was studied in modified mice FST. Mice were pretreated with a non-selective α-adrenergic receptor antagonist phenoxybenzamine, an α1/α2β-adrenergic receptor antagonist, prazosin, an α2-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT1/5-HT2 serotonergic receptor antagonist, methysergide, a non-selective 5-HT2 serotonergic receptor antagonist, cyproheptadine, nonselective muscarinic acetylcholine receptor antagonist, atropine, D2,D3,D4 dopamine receptor antagonist, haloperidol or γ-aminobutyric acid subunit A (GABAA) receptor antagonist, bicuculline. NmU-23 showed the antidepressant-like effects by decreasing the immobility time and increasing the climbing and swimming time. Prazosin, haloperidol, and bicuculline prevented the effects of NmU-23 on the climbing and swimming time. Methysergide and cyproheptadine prevented the effects of NmU-23 on the immobility, swimming and climbing time. Atropine prevented the effects of NmU-23 on the climbing time. Phenoxybenzamine, yohimbine and propranolol did not change the effects of NmU-23. The results demonstrated that the antidepressant-like effect of NmU-23 is mediated, at least in part, by an interaction of the α2-adrenergic, 5-HT1-2 serotonergic, D2,D3,D4 dopamine receptor, muscarinic acetylcholine receptors and γ-aminobutyric acid subunit A (GABAA) receptor in a modified mouse FST., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Present experiments focused on measuring the effect of neuropeptide SF (NPSF) on the hypothalamus-pituitary-adrenal (HPA) axis and behavior. The peptide was administered in different doses (0.25, 0.5, 1, 2 μg) intracerebroventricularly to rats, and the behavior of which was then observed by telemetry and open-field test. Effect of NPSF on core temperature was also measured via telemetry. Plasma ACTH and corticosterone concentrations were measured to assess the influence of NPSF on the HPA activation. In addition, the changes in corticotrophin-releasing hormone (CRH) level in the hypothalamic paraventricular nucleus were continuously monitored by means of intracerebral microdialysis. Our results showed that NPSF augmented paraventricular CRH release and increased ACTH and corticosterone levels in the plasma. The release of corticosterone was successfully blocked by the pre-treatment of the CRH antagonist α-helical CRH9-41. Spontaneous and exploratory locomotor activity was also stimulated according to the telemetric and open-field studies. However, NPSF only tended to alter stereotyped behavior in the open-field experiments. These results demonstrate that NPSF may play a physiologic role in the regulation of such circadian functions as the activity of motor centers and the HPA axis, through the release of CRH., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Peptide Neuromedin-U (NmU) is widely distributed in the central nervous system and the peripheral tissues. Its physiological effects include the regulation of blood pressure, heart rate, and body temperature, and the inhibition of gastric acid secretion. The action of NmU in rats is mediated by two G-protein-coupled receptors, NmU-1R and NmU-2R. NmU-2R is present mainly in the brain, and NmU-1R mainly in the periphery. Despite the great variety of the physiological action of NmU, little is known about its possible effects in different forms of behavior, such as anxiety. In the present work, NmU-23 (the rodent form of the peptide) was tested for its effect on anxiety in elevated plus maze test in mice. For detection of the possible involvement of neurotransmitters, the mice were pretreated with receptor blockers: haloperidol (a D2, dopamine receptor antagonist), propranolol (a β-adrenergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), phenoxybenzamine (a nonselective α-adrenergic receptor antagonist) or nitro-l-arginine (a nitric oxide synthase inhibitor). The peptide and nitro-l-arginine were administered into the lateral brain ventricle, while the receptor blockers were applied intraperitoneally. An NmU-23 dose 0.5μg elicited anxiolytic action, whereas this action is faded away when the dose was increased. For further testing therefore 0.5μg i.c.v. was used. Propranolol and atropine fully blocked the NmU-induced anxiolytic action, while haloperidol, phenoxybenzamine and nitro-l-arginine were ineffective. The results suggest that β-adrenergic and cholinergic mechanisms are involved in the anxiolytic action of NmU., (© 2013.)

The present experiments focused on the effects of neuromedin S on hypothalamic-pituitary-adrenal (HPA) activation and behavior. The peptide (0.25-1 nmol) was administered intracerebroventricularly to rats, the behavior of which was monitored by means of telemetry, open field observations and an elevated plus-maze (EPM) test. Autonomic functions such as the temperature and the heart rate were recorded by telemetry. The action on the HPA axis was assessed via measurements of the plasma corticosterone and ACTH levels. To reveal the transmission of the endocrine responses, animals were pretreated with corticotrophin releasing hormone receptor (CRHR) antagonists (1 nmol). In the open field test, the animals were pretreated with either a CRHR(1) antagonist (antalarmin) or haloperidol (10 microg/kg), while in the EPM test they were pretreated with antalarmin or diazepam (1 mg/kg). The dopamine release from striatal and amygdala slices after peptide treatment was measured with a superfusion apparatus. Neuromedin S exerted dose-dependent effects on the HPA system, which were inhibited by antalarmin. It also activated grooming and decreased the entries to and time spent in the open arms during the EPM test. The grooming response was abolished by haloperidol and antalarmin pretreatment, while diazepam and antalarmin showed a tendency to attenuate the response evoked in the EPM test. In the superfusion studies, neuromedin S enhanced the dopamine release from the amygdala slices. These results demonstrate that neuromedin S stimulates the HPA axis through the CRHR(1) pathway and evokes stereotyped behavior and anxiety through mesolimbic dopamine and corticotrophin releasing hormone release.

The effects of PACAP-38 on the extinction of active avoidance learning were studied in rats. The action of transmitter mediation was followed by pretreating the animals with appropriate receptor antagonists. PACAP-38 administered into the lateral brain ventricle caused a transitory facilitation of the extinction of a learned active avoidance response at 3 and 6 h following extinction, which had returned to or even above the control level at the 24-h testing. PACAP 6-38, which is an antagonist of PACAP-38, and an antibody against PACAP-38, prevented this action. When the animals were retested during a further 10 days, the control animals demonstrated response extinction on day 7, while the PACAP-38-treated animals still showed a high proportion (70%) of positive responses. The following receptor blockers diminished the action of PACAP-38 on the facilitation of extinction: propranolol, haloperidol, naloxone, bicuculline and nitro-L-arginine, the latter by blocking nitric oxide formation. Phenoxybenzamine and atropine were ineffective. The data reveal that the transitory action of PACAP-38 within 24 h on the facilitation of extinction is mediated by beta-adrenergic, dopaminergic, GABA-ergic and opiate receptors and nitric oxide. This transitory facilitated extinction is caused partly by depressed locomotion and presumably also an increased body temperature. Following a transitory facilitation of extinction from 24 h on, PACAP-38 demonstrated a greatly delayed extinction, which lasted for more than 7 days, while the control animals displayed complete extinction. The data suggest that PACAP-38 facilitates memory retrieval processes in the extinction of the active avoidance reflex.

The action of pituitary adenylate cyclase activating polypeptide (PACAP) 38 was tested in an open field 30 min, 3 h, 6 h and 24 h after icv PACAP 38 administration in rats. The effects on locomotion, rearing and grooming were measured. The possible roles of different receptors were tested in animals that had been pretreated with different receptor blockers followed by PACAP 38 administration. The locomotion, rearing and grooming activities were increased at 30 min, after PACAP 38 administration, whereas at 3 and 6 h there was no change in grooming, while the locomotion and rearing activities were sharply decreased. At 24 h after PACAP administration, there was no change in any of the parameters studied. PACAP antiserum, a PACAP antagonist (PACAP 6-38), haloperidol, phenoxybenzamine, propranolol and naloxone each prevented the changes observed at 30 min and 3 h. Atropine, nitro-l-arginine, bicuculline and methysergide were ineffective. The data demonstrate that the action of PACAP 38 on the open-field activity is regulated by D2, alpha- and beta-adrenergic and opiate receptors.

The mediation of orexin-A-induced hypothermia was investigated. Different doses of orexin-A (140-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and the colon temperature was used as an index of the thermoregulatory action. Orexin-A decreased both the basal colon temperature and the lipopolysaccharide-induced fever and exhibited a bell-shaped dose-response curve. I.c.v. pretreatment with neuropeptide Y (NPY) antiserum 24 h before orexin administration significantly decreased the hypothermic effect of orexin-A. These data strengthen the hypothesis that this appetite-regulating peptide might also play a role in thermoregulation, and its hypothermic effect seems to be mediated at least partially by NPY.

The action of orexin A on one-way passive avoidance learning was studied in rats. Orexin A administered into the lateral brain ventricle in conscious rats facilitated learning, the consolidation of learning and also retrieval processes in a dose-dependent manner in a passive avoidance paradigm. The involvement of transmitters was studied by pretreating the animals with receptor antagonists, which had proved to be effective with other neuropeptides in attenuating or blocking the action of orexin A. The following receptor blockers were used: haloperidol, phenoxybenzamine, propranolol, atropine, bicuculline, naloxone and nitro-L-arginine, which can block nitric oxide synthase. In the doses used all of the receptor blockers attenuated, but none of them fully blocked the action of orexin A on the consolidation of passive avoidance learning. The results demonstrate that orexin A is able to facilitate learning, consolidation of learning and also retrieval processes in a passive avoidance paradigm. A number of transmitters could be involved in the action of consolidation, but none of them is absolutely essential.

Background: Previous studies have demonstrated that centrally administered natriuretic peptides and pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) have hyperthermic properties. Isatin (indole-2, 3-dione) is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides. In this study the aim was to investigate the effects of isatin on thermoregulatory actions of PACAP-38, in rats., Results: One microg intracerebroventricular (icv.) injection of PACAP-38 had hyperthermic effect in male, Wistar rats, with an onset of the effect at 2 h and a decline by the 6th h after administration. Intraperitoneal (ip.) injection of different doses of isatin (25-50 mg/kg) significantly decreased the hyperthermic effect of 1 microg PACAP-38 (icv.), whereas 12.5 mg/kg isatin (ip.) had no inhibiting effect. Isatin alone did not modify the body temperature of the animals., Conclusion: The mechanisms that participate in the mediation of the PACAP-38-induced hyperthermia may be modified by isatin. The capability of isatin to antagonize the hyperthermia induced by all members of the natriuretic peptide family and by PACAP-38 makes it unlikely to be acting directly on receptors for natriuretic peptides or on those for PACAP in these hyperthermic processes.

The role of neuropeptide Y (NPY) in the mediation of orexin-induced hypothalamic-pituitary-adrenal (HPA) activation was investigated in the rat. The HPA system was stimulated by intracerebroventricular (i.c.v.) administration of orexin-A or orexin-B (140 or 280 pmol, respectively) and the plasma concentration of corticosterone was used as an index of the degree of activation. i.c.v. pretreatment with NPY antagonist or NPY antiserum (30 min or 24 h before orexin administration, respectively) inhibited the orexin-induced corticosterone release. The inhibitory actions of the antagonist and the antiserum were revealed by the dose-response curve; the highest concentrations practically abolished the HPA activation evoked by the orexins. These data suggest that the HPA system-stimulating effect of the orexins may be mediated by NPY.

The effects of the recently identified neuropeptides orexin-A and orexin-B on the hypothalamic-pituitary-adrenal (HPA) system were investigated. An in vivo system was used to assess the central effects of both orexin-A and orexin-B. Different doses of the orexins (2.8-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and plasma corticosterone was used as an index of the degree of the activation of the HPA system. Both peptides exhibited a clear dose-response action, although orexin-B proved to be less effective than orexin-A. Pretreatment with the corticotropin-releasing hormone (CRH) antagonist alpha-helical CRH9-41 completely prevented the action of the orexins. Orexin-A, orexin-B or adrenocorticotropic hormone (ACTH) was further administered intraperitoneally (i.p.). While ACTH evoked a significant adrenal response, the orexins did not influence the basal secretion. Adrenal slices, oxygenized and perifused with Krebs' solution, were also treated with orexin-A, orexin-B or ACTH. Both orexins failed to modify the release of corticosterone, but ACTH induced a marked adrenal response. This study suggests that these appetite-regulating peptides might activate the HPA system at a central level but neither orexin-A nor orexin-B appears to modulate directly the adrenal corticosterone release.

In the present study, the action of PACAP 38 on one-way passive avoidance learning was investigated. PACAP-38 was administered into the lateral brain ventricle and the latency of the passive avoidance response was measured 24 h later. In order to study the possible roles of various neurotransmitters in mediating the action of PACAP on the consolidation of passive avoidance learning, the animals were pre-treated with receptor blockers in doses that per se proved to be ineffective. PACAP facilitated the learning, the consolidation of learning and the retrieval of the passive avoidance response. The following receptor blockers attenuated the action of PACAP on this consolidation: haloperidol, phenoxybenzamine, propranolol and methysergide. An antagonist of PACAP 38, PACAP 6-38, and also nitro-L-arginine (the latter blocks the enzyme nitric oxide synthase) thereby inhibiting the formation of NO from L-arginine, completely blocked the action of PACAP 38 on consolidation. The following receptor blockers were ineffective: naloxone, bicuculline and atropine. The presented data suggest that PACAP 38 is able to improve the learning and memory processes in a passive avoidance paradigm. In this action, the PACAP 38 receptor and NO are important mediators. Dopaminergic, alpha- and beta-adrenergic mediation and serotonin receptors modified the action of PACAP 38, but they are probably not of great importance.

The effects of centrally administered pituitary adenylate cyclase-activating polypeptide (PACAP-38) on body temperature were investigated in rats. Intracerebroventricular (i.c.v.) administration of PACAP-38 in doses of 500 and 1000 ng induced a dose-related elevation in colon temperature 2, 3, 4, 5 and 6 h after injection. The i.c.v. pretreatment of the animals with different dilutions of PACAP-38 antiserum prevented the development of hyperthermia in PACAP-38-treated animals, whereas PACAP-38 antiserum alone did not modify the colon temperature. An intramuscular injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the PACAP-38-induced hyperthermia. Our data indicate that PACAP may induce hyperthermia via the central nervous system, and this hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.

Several data suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in the regulation of local circulation. One possible role of PACAP in the regulation of circulation is that, it may modify the cyclooxygenase pathway of the arachidonate cascade in platelets. Our study was designed to study the effect of PACAP on the cyclooxygenase pathway of rat platelets and on platelet aggregation. PACAP (10(-7) and 10(-6) M) significantly inhibited the cyclooxygenase pathway of platelets, mostly the thromboxane synthesis. Pretreatment with a PACAP receptor antagonist, PACAP(6-38), or with an inhibitor of protein kinase A, H-89, shows that the effects of PACAP on the cyclooxygenase pathway were diminished. In the aggregation studies, PACAP inhibited both the arachidonic acid-induced and the thrombin-induced platelet aggregation. It can be concluded that PACAP inhibits the cyclooxygenase pathway of rat platelets via a specific PACAP receptor-activated, cAMP-dependent pathway, and these effects of PACAP are involved in the inhibition of platelet aggregation.

The presence of nerve endings containing pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) around cerebral microvessels suggests that these peptides have regulatory roles in the cerebral microcirculation. Prostanoids synthesized by the cerebrovascular endothelium have a determining role in the regulation of the brain circulation. In the present study, the effects of PACAP and VIP on the cyclooxygenase pathway of cerebral microvessels were investigated. The isolated microvessels were incubated with 1-14C-arachidonic acid and different concentrations of the peptides. The prostanoids formed were separated by means of overpressure thin-layer chromatography, and were quantitatively determined by liquid scintillation. Higher concentrations (10-7 and 10-6 mol L-1) of PACAP significantly inhibited the activity of the cyclooxygenase pathway, whereas VIP had no significant effect on it. As regards the cyclooxygenase metabolites, the syntheses of thromboxane A2 and prostaglandin D2 were inhibited significantly. PACAP and VIP are known to increase the intracellular cAMP level in the cerebral microvessels and in the present experiments the protein kinase A inhibitor H-89 attenuated the effect of PACAP on prostanoid synthesis. It is concluded that the cyclooxygenase pathway of rat cerebral microvessels is more sensitive to PACAP than to VIP. The inhibitory effect of PACAP on prostanoid synthesis is mediated via a cAMP-dependent pathway. By inhibiting the formation of vasoactive prostanoids, PACAP can decrease the vasoreactivity of the microvessels.

This review summarizes the action of atrial natriuretic (ANP) and some related compounds such as BNP, CNP and fragments on the central nervous system, based mainly on the results obtained in the author's laboratory. The aim of the investigations was to assess the physiological significance of the natriuretic peptide family in the brain by administering the peptides into the lateral brain ventricle. Effects were studied on motivated behavior, including active and passive avoidance learning, food-reinforced conditioning, open-field activity, electroshock-induced amnesia, development of morphine tolerance and dependence, and picrotoxin-kindled seizure syndrome. Antisera against ANP were used in order to follow the specificity of the resulting action. The role of neurotransmitters in the mediation of peptide action was elucidated by treating the animals with receptor blockers before peptide administration.

Galanin (2000, 1000 ng) administered into the lateral brain ventricle decreased the severity of picrotoxin-kindled convulsions in rats. The bilateral injection (200, 100 and 50 ng) of galanin into the hippocampus also evoked an anticonvulsive effect. When administered into the caudate nuclei or substantia nigra reticulata, galanin exerted anticonvulsive action only in a high dose (200 ng), whereas in the nucleus accumbens it did so in a low dose (50 ng). When administered into the ventral tegmental area in a dose of 50, 100 or 200 ng galanin failed to reduce the manifestations of picrotoxin-kindled seizures.

The effects of certain neuropeptides on electroconvulsive (ECS) shock-induced amnesia were studied in rats. The ECS was applied immediately after the learning a one-trial passive avoidance paradigm. The peptides--rat atrial natriuretic peptide (rANP 1-28, ANP), porcine brain natriuretic peptide (pBNP 1-32, BNP), rat calcitonin gene-related peptide (CGRP) and bombesin--were injected into the lateral brain ventricle 30 min after the ECS. In order to study the possible role of neurotransmitters in mediating the action of the peptides on amnesia, the animals were treated immediately after the ECS with, doses which themselves did not modify either the learning itself or the amnesic action of the ECS. All the above peptides attenuated the ECS-induced amnesia, but the transmitters involved in these actions differed. The anticonvulsive action of ANP was prevented by haloperidol (10 micrograms/kg i. p.), propranolol (10 mg/kg i. p.) and atropine (2 mg/kg i. p.). Phenoxybenzamine (2.0 mg/kg i. p.), bicuculline (1 mg/kg i. p.), methysergide (5 mg/kg i. p.) and naloxone (0.3 mg/kg i. p.) had no effect. Besides alpha-adrenergic and cholinergic receptor blockers the beta-adrenergic blocker propranolol was also effective in preventing the antiamnesic action of the BNP. As concerns the action of bombesin, only haloperidol was effective. Alpha- and beta-adrenergic and cholinergic receptor blockers and opiates are involved in the antiamnesic properties of CGRP. The results showed that, despite the fact that the studied, peptides attenuated the ECS-induced amnesia, different transmitters are involved in their action.

The presence of FMRFamide (Phe-Met-Arg-Phe-amide)-like immunoreactivity in neuronal elements in the hypothalamus suggested a role for this in the hypothalamic control of the anterior pituitary function. We report here the action of FMRFamide on growth hormone release following intracerebroventricular administration to rats. The injection of 200 ng (313.8 picomoles) of FMRFamide (in 2 ul) produced a significantly increased plasma GH 15 min after injection. The GH-increasing effect of 400-800 ng (627-1255 picomoles) of FMRFamide was already developed after 5 min and lasted up to 30 min. No change was detected in the plasma FSH, LH and prolactin levels at any time during the experimental period. The intravenous administration of 10, 30 or 100 ug of FMRFamide had no effect on the plasma GH level. We conclude that FMRFamide can act at low doses to increase GH release through the inhibition of somatostatin release or the stimulation of GRF. We could not exclude a direct site of action in the pituitaries.

The effects of FMRFamide on passive avoidance behaviour and electroshock-induced amnesia following intracerebroventricular administration were studied in rats. FMRFamide given immediately after the learning trial, or 20 min before the retention trial, attenuated the avoidance response, thereby impairing the consolidation and retrieval processes. Electroshock induced amnesia when applied immediately after the learning trial. Treatment with FMRFamide facilitated the amnesia of the passive avoidance response. The results indicate that FMRFamide peptide belongs in the class of neuropeptide which are amnesic.

Abstract: The action of ghrelin on telemetrically recorded motor activity and the transmission of the effects of this neuropeptide on spontaneous and exploratory motor activity and some related endocrine and homeostatic parameters were investigated. Different doses (0.5–5 μg) of ghrelin administered intracerebroventricularly caused significant increases in both square crossing and rearing activity in the “open-field” apparatus, while only the dose of 5 μg evoked a significant increase in the spontaneous locomotor activity recorded by telemetry. Ghrelin also induced significant increases in corticosterone release and core temperature. To determine the transmission of these neuroendocrine actions, the rats were pretreated with different antagonists, such as a corticotropin-releasing hormone (CRH) antagonist (α-helical CRH9–41), the nitric oxide synthase inhibitor Nω-nitro-l-arginine-methyl ester (l-NAME), haloperidol, cyproheptadine or the cyclooxygenase inhibitor noraminophenazone (NAP). The open-field and biotelemetric observations revealed that the motor responses were diminished by pretreatment with the CRH antagonist and haloperidol. In the case of HPA (hypothalamic pituitary adrenal) activation, only cyproheptadine pretreatment proved effective; haloperidol and l-NAME did not modify the corticosterone response. NAP had only a transient, while cyproheptadine elicited a more permanent impact on the hyperthermic response evoked by ghrelin; the other antagonists proved to be ineffective. The present data suggest that both CRH release and dopaminergic transmission may be involved in the ghrelin-evoked behavioral responses. On the other hand, ghrelin appears to have an impact on the HPA response via a serotonergic pathway and on the hyperthermic response via a cyclooxygenase and a serotonergic pathway. [Copyright &y& Elsevier]