GABAA receptors in nucleus accumbens shell mediate the hyperphagia and weight gain following haloperidol treatment in rats.
OBJECTIVE
Weight gain is a common outcome of antipsychotics therapy in schizophrenic patients. However, the underlying neuronal mechanisms are unclear. The present study was undertaken to investigate the role of GABA(A) receptors within the framework of nucleus accumbens shell (AcbSh) in haloperidol-induced hyperphagia and body weight gain in sated rats.


METHODS
In acute studies, GABA(A) receptor agonists muscimol, diazepam or antagonist bicuculline were administered by AcbSh route, alone or in combination with haloperidol (intraperitoneal/ip). Immediately after these treatments, preweighed food was offered to the animals at commencement of dark phase. Cumulative food intake was measured at 2 and 6 h post-injection time-points. Furthermore, effects of subacute haloperidol treatment, alone or in combination with muscimol, diazepam or bicuculline, on food intake and body weight were investigated.


RESULTS
While acute treatment with haloperidol, muscimol or diazepam dose dependently stimulated the food intake, bicuculline suppressed the same. Prior administration of muscimol (20 ng/rat, intra-AcbSh) and diazepam (5 microg/rat, intra-AcbSh) significantly potentiated, whereas bicuculline (40 ng/rat, intra-AcbSh) negated the hyperphagic effect of acute haloperidol (0.005 or 0.01 mg/kg/rat, ip). Subacute administration of haloperidol (0.01 mg/kg/rat/day, ip) for 15 days produced increase in food intake and body weight. Although, concomitant administration of muscimol (20 ng/rat/day, intra-AcbSh) or diazepam (5 microg/rat/day, intra-AcbSh) markedly enhanced, bicuculline (40 ng/rat/day, intra-AcbSh) prevented the subacute haloperidol-induced hyperphagia and weight gain.


CONCLUSIONS
The results of present study suggest that increased food intake and body weight following haloperidol treatment in rats, may be mediated via AcbSh GABA(A) receptors.
Meena
Harsahay
H
Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Amravati Road, Nagpur, Maharashtra, 440 033, India.
Nakhate
Kartik T
KT
Kokare
Dadasaheb M
DM
Subhedar
Nishikant K
NK
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006220:Haloperidol / Q000009:adverse effects*; D006963:Hyperphagia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006220:Haloperidol