Involvement of 5-hydroxytryptamine 2A (5-HT2A) receptors in the mediation of the discriminative stimulus properties of (+/-)DOI in rats.
Rats were trained to discriminate between the 5-HT2A/2C receptor agonist (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI, 0.35 mg/kg] and saline using a two-lever drug discrimination procedure; afterwards, the effects of different 5-HT agonists and antagonists on the discriminative stimulus properties induced by (+/-)DOI were studied. In substitution tests, D-lysergic acid diethylamide (LSD, 0.02 and 0.04 mg/kg) and quipazine (0.5, 1.5 and 3 mg/kg), 5-HT2A/2C agonists, evoked dose-related responses to the (+/-)DOI-appropriate lever, while the non-selective 5-HT agonist 1-(3-chlorophenyl)piperazine (m-CPP, 0.1, 0.5 and 1 mg/kg), which has the highest binding affinity for 5-HT2C receptors, failed to show substitution. In antagonist studies, the discriminative stimulus effect of (+/-)DOI was completely antagonized by ketanserin (0.5 mg/kg) and cyproheptadine (0.5 mg/kg), preferential 5-HT2A receptor antagonists, and partially by the 5-HT2A/2C receptor antagonist mesulergine (0.25, 0.5 and 1.0 mg/kg) and the 5-HT2A/D2 antagonist spiperone (0.025, 0.05 and 0.1 mg/kg). The above data suggest that the discriminative stimulus effects of (+/-)DOI are predominantly mediated by 5-HT2A receptors.
Chojnacka-Wójcik
E
E
Department of New Drug Research, Polish Academy of Sciences, Kraków, Poland.
Kłodzińska
A
A
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005793:Generalization, Psychological / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology
D000662:Amphetamines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012965:Sodium Chloride; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine