Antagonism by the 5-HT2A/C receptor agonist DOI of raclopride-induced catalepsy in the rat.
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.
Wadenberg
M L
ML
Department of Behavioral Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Ahlenius
S
S
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000662:Amphetamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D008297:Male; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology; D012457:Salicylamides; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D015031:Zimeldine / Q000494:pharmacology
D006916:5-Hydroxytryptophan; D000662:Amphetamines; D001545:Benserazide; D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D020891:Raclopride; D016713:Ritanserin; D012457:Salicylamides; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D015031:Zimeldine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine