The stimulus effects of 8-OH-DPAT: evidence for a 5-HT2A receptor-mediated component.
A previous investigation in our laboratory found that the stimulus effects of the 5-HT2A agonist, LSD, are potentiated by 5-HT1A receptor agonists including the prototypic agonist, 8-OH-DPAT. Also suggestive of behaviorally relevant interactions between 5-HT1A and 5-HT2A receptors are behavioral analyses of locomotor activity, head-twitch response, forepaw treading and production of the serotonin syndrome; in some instances effects are augmented, in other, diminished. These observations led us in the present investigation to test the hypothesis that stimulus control by 8-OH-DPAT [0.2 mg/kg; 15 min pretreatment time] is modulated by 5-HT2A ligands. Stimulus control was established with 8-OH-DPAT in a group of 10 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. As shown previously, stimulus control by 8-OH-DPAT and the generalization of 8-OH-DPAT to the 5-HT1A partial agonist, buspirone, was completely blocked by the selective 5-HT1A antagonist, WAY-100635. In contrast, antagonism by the selective 5-HT2A antagonist, M100907 [0.1 mg/kg; 30 min pretreatment time], of 8-OH-DPAT and of the generalization of 8-OH-DPAT to buspirone was statistically significant but less than complete. In light of our previous conclusions regarding the interactions of 5-HT1A agonists with LSD-induced stimulus control, the present data suggest that the interaction between 5-HT1A and 5-HT2A receptors is bidirectional in drug discrimination studies.
Reissig
C J
CJ
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214-3000, USA.
Eckler
J R
JR
Rabin
R A
RA
Rice
K C
KC
Winter
J C
JC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D005464:Fluorobenzenes; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide; C079049:volinanserin; D002065:Buspirone