OPERANT RESPONSE SUPPRESSION INDUCED WITH SYSTEMIC ADMINISTRATION OF 5-HYDROXYTRYPTOPHAN IS CENTRALLY MEDIATED

Intracerebroventricular (ICV) administration of selective serotonergic agents was used to examine the extent of central mediation of 5-HTP-i nduced operant response suppression in rats. ICV administration of LY5 3857 (1.0, 3.75, or 7.5 mu g/5 mu l/5 min) dose dependently blocked re sponse suppression induced with systemically administered 5-HTP (25 mg /kg, IP), whereas ICV 0.9% saline (5 mu l over 5 min) had no significa nt effect on 5-HTP-induced response suppression. ICV ketanserin (7.5 m u g/5 mu l/5 min) also blocked response suppression induced with syste mically administered 5-HTP. ICV administration of the 5-HT2A/2C recept or agonist DOI (80 mu g/5 mu l/5 min) induced significant periods of r esponse suppression in this model, which was blocked with LY53857 (1.0 mg/kg, IF) pretreatment. These data demonstrate that central administ ration of 5-HT2A/2C antagonists potently attenuate operant response su ppression induced with systemically administered 5-HTP or DOI and are in agreement with previous findings suggesting central mediation of 5- HTP-induced operant response suppression.