Behavioural evidence for a functional interaction between central 5‐HT2 and 5‐HT1A receptors

• Published in: British journal of pharmacology Vol. 100; no. 4; pp. 793 - 799
• Main Authors: Backus, Lisa I., Sharp, Trevor, Grahame‐Smith, David G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1990; Nature Publishing
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Apomorphine - pharmacology; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Central Nervous System - drug effects; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Haloperidol - pharmacology; Ketanserin - pharmacology; Male; Methoxydimethyltryptamines - pharmacology; Neurotransmission and behavior; Piperidines - pharmacology; Prazosin - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Pyrimidines - pharmacology; Quinolines - pharmacology; Rats; Rats, Inbred Strains; Receptors, Serotonin - drug effects; Ritanserin; Serotonin - pharmacology; Stereotyped Behavior - drug effects; Tetrahydronaphthalenes - pharmacology; Rat; Serotonin; Serotonin antagonist; Rodentia; S2 receptor; Central nervous system; Stereotype; Binding site; Serotonin agonist; S1 receptor; Skaking behaviour; Vertebrata; Mammalia; Binding capacity; Animal; Behavior; Neurotransmission
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb14094.x

1 The possibility of 5‐HT2 receptor modulation of central 5‐HT1A receptor function has been examined using the 5‐hydroxytryptamine (5‐HT) behavioural syndrome induced by 5‐HT1A receptor active drugs in rats. 2 The 5‐HT2/5‐HT1C antagonist ritanserin (0.1–2 mg kg−1) increased the 5‐HT behavioural syndrome induced by submaximally effective doses of 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT) and gepirone. 3 Pretreatment with the 5‐HT2/5‐HT1C antagonist ICI 170,809 (0.25–5 mg kg−1) also enhanced the behavioural syndrome induced by 8‐OH‐DPAT or 5‐MeODMT. 4 The 5‐HT2/α1‐adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg−1) significantly increased the 5‐HT behavioural syndrome induced by 8‐OH‐DPAT or 5‐MeODMT, while in a higher dose (2.5 mg kg−1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5‐HT behavioural syndrome through blockade of α1‐adrenoceptors. 5 Ritanserin and ICI 170,809 had no effect on apomorphine‐induced stereotypy or hyperactivity, indicating that these drugs do not produce non‐specific behavioural activation. 6 Ritanserin and ICI 170,809 inhibited quipazine‐induced wet dog shakes at doses similar to those enhancing the 5‐HT behavioural syndrome. 7 We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5‐HT1A agonist‐induced behaviour through blockade of an inhibitory 5‐HT2 receptor regulating or coupled to 5‐HT1A receptor‐mediated function.