title: Neurotransmitter-mediated anxiogenic action of PACAP-38 in rats.
abstract: The action of PACAP-38 was studied by measuring the anxiogenic-anxiolytic behavior of rats in an elevated plus maze. PACAP-38 was administered into the lateral brain ventricle and the behavior of the animals was measured 3h later. The possible involvement of transmitters was measured by pretreating the animals with receptor blockers which alone did not influence the task, but in the doses used were effective with other neuropeptides. The receptor antagonist PACAP 6-38 (a PAC 1/VPAC2 receptor antagonist of PACAP-38 receptor), haloperidol (a non-selective dopamine receptor antagonist), phenoxybenzamine (an α1/α2β-adrenergic receptor antagonist), propranolol(a β-adrenergic receptor antagonist), bicuculline (a gamma-aminobutyric acid subunit A receptor antagonist), methysergide (a nonselective 5-HT2 serotonergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), naloxone (a nonselective opioid receptor antagonist) and nitro-l-arginine which acts by blocking the enzyme nitric oxide synthase, thereby blocking the nitric oxide synthesis, were tested. The following parameters were measured: the time spent in open arms/the time spent in total entries. PACAP-38 decreased the ratio of time spent in open arms to the time spent in total entries, indicating anxiogenic action. The total number of entries was not altered significantly either by PACAP-38 or by the receptor blockers. The following receptor blockers diminished the action of PACAP-38: PACAP 6-38,haloperidol, methysergide, naloxone and nitro-l-arginine. Pretreatment with atropine, phenoxybenzamine, propranolol and bicuculline did not influence the action of PACAP-38 on the time spent in open arms. The results demonstrate that PACAP-38 administered into the lateral brain ventricle exerted anxiogenic action at 3 h following treatment. Pretreatment of the animals with various receptor blockers indicated that a nonselective dopaminergic receptor antagonist, 5HT2 serotonergic and opioid receptors, nitric oxide and PAC1 receptors are involved in the anxiogenic action induced by PACAP-38.
authors.affiliation: Department of Pathophysiology, Hungarian Academy of Sciences, University of Szeged, H-6701 Szeged, Hungary; MTA-SZTE Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged, H-6701 Szeged, Hungary. Electronic address: Telegdy.Gyula@med.u-szeged.hu.
authors.forename: G
authors.initials: G
authors.lastname: Telegdy
authors.affiliation: MTA-SZTE Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged, H-6701 Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Adamik
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008784:Methysergide / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism* / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: D018674:Adrenergic Antagonists; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D009603:Nitroso Compounds; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018079:Receptors, GABA; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D058830:Serotonin 5-HT2 Receptor Antagonists; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D010643:Phenoxybenzamine; C084185:N-nitrosoarginine; D009270:Naloxone; D001285:Atropine; D001120:Arginine; D011433:Propranolol; D006220:Haloperidol; D008784:Methysergide; D001640:Bicuculline
keywords: Anxiety; Male rats; Neurotransmitter mediation; PACAP-38