title: Effects of pituitary adenylate cyclase polypeptide (PACAP) on extinction of active avoidance learning in rats: involvement of neurotransmitters.
abstract: 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.
authors.affiliation: Institute Pathophysiology, University of Szeged, Neurohumoral Research Group of the Hungarian Academy of Sciences, H-6701 Szeged, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Adamik
authors.forename: Gyula
authors.initials: G
authors.lastname: Telegdy
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: C495403:Adcyap1 protein, rat; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D009292:Narcotic Antagonists; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D019335:Nitroarginine; D009270:Naloxone; D011433:Propranolol; D006220:Haloperidol; D001640:Bicuculline