Neurochemical effects of 5-HT1 receptor ligands in pigeons

• Published in: European journal of pharmacology Vol. 229; no. 2-3; p. 109
• Main Authors: Gleeson, S, Weissman, B A, Seggel, M R, Barrett, J E
• Format: Journal Article
• Language: English
• Published: Netherlands 15-12-1992
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - metabolism; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Binding Sites; Brain - metabolism; Columbidae; Hydroxyindoleacetic Acid - cerebrospinal fluid; Indoles - pharmacology; Male; Methoxyhydroxyphenylglycol - cerebrospinal fluid; Piperazines - pharmacology; Receptors, Serotonin - metabolism; Serotonin - cerebrospinal fluid; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(92)90543-D

Pigeon cerebrospinal fluid was assayed for 5-HT (5-hydroxytryptamine) and catecholamine metabolites after systemic drug injection. The 5-HT1-like receptor agonists 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), and 1-(3-chlorphenyl)piperazine (mCPP) decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) without altering other metabolites. 5-HIAA decreases occurred at doses of 8-OH-DPAT and RU 24969 that have anti-conflict effects in pigeons, whereas TFMPP and mCPP decreased 5-HIAA only at behaviorally disruptive doses. The novel compound 1-(2-methoxyphenyl)-1-(4-(2-phthalimido)butyl)piperazine (NAN-190), a putative 5-HT1A receptor antagonist, did not affect 5-HIAA, but attenuated the decreases produced by the agonists. NAN-190 and the alpha 1-adrenoceptor antagonist prazosin increased levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol and had additive effects when co-administered. The rank order of potency in inhibiting [3H]8-OH-DPAT binding in pigeon cerebrum was 8-OH-DPAT = RU 24969 > NAN-190 >> mCPP > TFMPP. The results support suggestions that decreased 5-HT neurotransmission underlies the anxiolytic-like effects of 5-HT1A receptor agonists in pigeons.