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-induced operant response suppression in rats. ICV administration of LY53857 (1.0, 3.75, or 7.5 μg/5 μl/5 min) dose dependently blocked response suppression induced with systemically administered 5-HTP (25 mg/kg, IP), whereas ICV 0.9% saline (5 μl over 5 min) had no significant effect on 5-HTP-induced response suppression. ICV ketanserin (7.5 μg/5 μl/5 min) also blocked response suppression induced with systemically administered 5-HTP. ICV administration of the 5- HT 2 A 2 C receptor agonist DOI (80 μg/5 μl/5 min) induced significant periods of response suppression in this model, which was blocked with LY53857 (1.0 mg/kg, IP) pretreatment. These data demonstrate that central administration of 5- HT 2 A 2 C antagonists potently attenuate operant response suppression 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.