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Rimonabant enhances clozapine‐induced neurochemical and histochemical responses in the rat
Author(s) -
Menezes Michelle M,
Davis Richard J.,
Johnson Kandis L.,
Sundquist Sarah J.,
Nomikos George G.,
Nisenbaum Laura K.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb114-a
Subject(s) - rimonabant , clozapine , neurochemical , atypical antipsychotic , pharmacology , nucleus accumbens , chemistry , dopamine , endocrinology , medicine , antagonist , antipsychotic , schizophrenia (object oriented programming) , cannabinoid receptor , receptor , psychiatry
Acute administration of atypical antipsychotic drugs, such as clozapine, produces an increase in the efflux of catecholamines preferentially in the prefrontal cortex (PFC) and a characteristic expression of Fos‐like immunoreactivity (Fos‐li) in the forebrain of experimental animals. We examined the effects of the CB‐1 receptor antagonist rimonabant on clozapine‐induced increases in the efflux of dopamine (DA) and norepinephrine (NE) in the PFC, and Fos‐li in the PFC, nucleus accumbens shell (NAc‐shell) and core (NAc‐core) and dorsolateral striatum (DL‐Str) in the rat. Rimonabant and clozapine dose‐dependently increased cortical efflux of DA and NE. Pretreatment (30min) with rimonabant (3mg/kg, IP) significantly enhanced the clozapine (10mg/kg, SC)‐induced increase in catecholamine efflux in the PFC. Clozapine (8mg/kg, SC) significantly increased the Fos‐li in the PFC and NAc‐shell. Rimonabant (10mg/kg, IP) significantly increased the Fos‐li in the PFC. Rimonabant pretreatment (30min) significantly enhanced the clozapine‐induced Fos‐li in the PFC and NAc‐shell. Clozapine alone and the combination of rimonabant and clozapine demonstrated a positive atypical index (based on the difference in the Fos‐li in the NAc‐shell versus the DL‐Str) indicating atypicality of antipsychotic‐like activity. The present results indicate that rimonabant enhances the neurochemical and histochemical effects of clozapine and that this combined administration reveals an atypical antipsychotic‐like profile of drug action. Funded by: Eli Lilly and Co.