Aripiprazole (OPC-14597) fully substitutes for the 5-HT1A receptor agonist LY293284 in the drug discrimination assay in rats.

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Marona-Lewicka D, Nichols DE

Aripiprazole (OPC-14597) fully substitutes for the 5-HT1A receptor agonist LY293284 in the drug discrimination assay in rats.

Psychopharmacology (Berl). 2004 Apr;172(4):415-21. Epub 2003 Nov 28.

PubMed ID

14647959 [ View in PubMed

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Abstract

RATIONALE: Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug with a low incidence of side effects. The therapeutic action of aripiprazole has been attributed to its unique agonist/antagonist effects at D(2) dopamine receptors; however, aripiprazole also has significant in vitro affinity at 5-HT(1A) receptors. OBJECTIVES: The 5-HT(1A) agonist property of aripiprazole has so far not been evaluated in any in vivo assay. METHODS: Thirteen male Sprague Dawley rats trained to discriminate the 5-HT(1A) agonist LY 293284 (75 nmol/kg) from saline, using a fixed ratio (FR) 50 schedule of food-reinforcement in a two-lever operant-conditioning task, were used to evaluate the behavioral effect of aripiprazole at 5-HT(1A) receptors. RESULTS: Aripiprazole fully mimicked LY 293284 in a drug-discrimination assay with an ED(50) of 1.39 micromol/kg (0.62 mg/kg). In combination tests, aripiprazole did not block the LY 293284 cue but at 8.92 micromol/kg (4 mg/kg) significantly reduced the response rate by lowering the threshold for induction of the 5-HT syndrome produced by the training dose of LY 293284. Moreover, the selective 5HT(1A) receptor antagonist WAY 100635 was able to block the substitution of aripiprazole in LY-293284 trained rats. CONCLUSION: Although the efficacy of aripiprazole against the positive symptoms of schizophrenia may be related to its dopamine receptor interactions, it seems possible that its atypical profile may derive, at least in part, from its 5-HT(1A) agonist effect, rather than from unusual D(2) receptor properties.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aripiprazole	5-hydroxytryptamine receptor 1A	Protein	Humans	Unknown	Partial agonist	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 1A	Protein	Humans	Yes	Partial agonist	Details