ANTAGONISM BY THE 5-HT2A C RECEPTOR AGONIST DOI OF RACLOPRIDE-INDUCEDCATALEPSY IN THE RAT/

It has been shown that the administration of 5-hydroxytryptamine (5-HT )(1A) receptor agonists will antagonize the catalepsy induced by dopam ine D-1 or D-2 receptor blocking agents. In the present study, adminis tration of the 5-HT2A/C receptor agonist, 1-(2,5-dimethoxy-4-iodo)-2-a minopropane (DOI) (1 mg kg(-1) s.c.), counteracted the catalepsy produ ced by the dopamine D-2 receptor antagonist, raclopride (16 mgr kg(-1) s.c.), but not by the dopamine D-1 receptor antagonist, 8-chloro-2,3, 4,5-tetra-hydro-3-methyl-5-phenyl-1H- 3-benzaze (SCH 23390) (0.2 mg kg (-1) s.c.). The effects of DOI on raclopride-induced catalepsy were fu lly antagonized by pretreatment with the 5-HT2A/C receptor antagonist, ritanserin (2 mg kg(-1) s.c.). The 5-HT precursor, 5-hydroxytryptopha n (5-HTP) (6.25-25.0 mg kg(-1) i.p.), in combination with the peripher al 5-HTP decarboxylase inhibitor, benserazide (25 mg kg(-1) i.p.), and the selective serotonin reuptake inhibitor, zimeldine (10 mg kg(-1) s .c.), enhanced the catalepsy produced by a low dose of raclopride (4 m g kg(-1) s.c.). It is concluded that stimulation of (postsynaptic) 5-H T2 receptors results in antagonism of the catalepsy induced by treatme nt with a dopamine D-2, but not a D-1, receptor antagonist. The fact t hat 5-HTP, in the presence of benserazide and zimeldine, enhanced racl opride-induced catalepsy suggests the possibility of postsynaptic 5-HT receptors acting in opposition to the 5-HT1 and 5-HT2 receptors, as r egards extrapyramidal motor functions in the rat.