It has been shown that the administration of
5-hydroxytryptamine (5-HT)1A receptor agonists will antagonize the
catalepsy induced by
dopamine D1 or D2 receptor blocking agents. In the present study, administration of the 5-HT2A/C receptor agonist, 1-(2,5-dimethoxy-4-iodo)-2-aminopropane (DOI) (1 mg kg-1 s.c.), counteracted the
catalepsy produced by the
dopamine D2 receptor antagonist,
raclopride (16 mg kg-1 s.c.), but not by the
dopamine D1 receptor antagonist (R)-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepine (
SCH 23390) (0.2 mg kg-1 s.c.). The effects of DOI on
raclopride-induced
catalepsy were fully antagonized by pretreatment with the 5-HT2A/C receptor antagonist,
ritanserin (2 mg kg-1 s.c.). The
5-HT precursor,
5-hydroxytryptophan (5-HTP) (6.25-25.0 mg kg-1 i.p.), in combination with the peripheral
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 mg kg-1 s.c.). It is concluded that stimulation of (postsynaptic) 5-HT2 receptors results in antagonism of the
catalepsy induced by treatment with a
dopamine D2, but not a D1, receptor antagonist. The fact that
5-HTP, in the presence of
benserazide and
zimeldine, enhanced
raclopride-induced
catalepsy suggests the possibility of postsynaptic
5-HT receptors acting in opposition to the 5-HT1 and 5-HT2 receptors, as regards extrapyramidal motor functions in the rat.