Possible involvement of dopamine D‐1 and D‐2 receptors in diazepam‐induced hyperphagia in rats

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Abstract
Summary:Possible involvement of dopamine receptors in diazepam‐induced (1 mg/kg, subcutaneous (sc)) hyperphagia was studied in nondeprived rats. Pretreatment with the selective D‐1 antagonist, SCH23390 (0.03 mg/kg, sc) inhibited diazepam‐induced hyperphagia. In addition, pretreatment with the preferential D‐2 antagonists, haloperidol (0.1 to 0.3 mg/kg, sc) and clebopride (0.1 to 0.3 mg/kg, sc) inhibited diazepaminduced hyperphagia in a dose‐dependent manner. Pretreatment with co‐administration of SCH23390 (0.01 mg/kg, sc) and clebopride (0.03 mg/kg, sc) completely inhibited this hyperphagia. The selective D‐2 antagonist, sulpiride (40 mg/kg, sc) and the peripheral D‐2 antagonist, domperidone (10 mg/kg, sc) did not affect diazepam‐induced hyperphagia. However, sulpiride (10 μg, icv) or domperidone (2 μg, icv) administered centrally inhibited this hyperphagia. The highest dose of haloperidol (0.3 mg/kg, sc) or clebopride (0.3mg/kg, sc) and higher doses of SCH23390 (0.01 and 0.03 mg/kg, sc) or SCH23390/clebopride (0.01/0.03 and 0.01/0.1 mg/kg, sc) tended to decrease spontaneous feeding in non‐deprived rats. In addition, the highest dose of haloperidol, clebopride or SCH23390/clebopride inhibited spontaneous feeding in deprived rats. Interestingly, diazepam‐induced hyperphagia was inhibited significantly by doses of haloperidol (0.1 mg/kg, sc), clebopride (0.1 mg/kg, sc) and SCH23390/clebopide (0.003/0.03 and 0.003/0.1 mg/kg, sc) which did not affect spontaneous feeding in non‐deprived or deprived rats. Pretreatment with α‐methyl‐p‐tyrosine (40 mg/kg, IP × 2, 6 and 2 h prior to diazepam administration) failed to inhibit this hyperphagia. Furthermore, pretreatment with a large dose of haloperidol (5 mg/kg, sc, 4 days before diazepam administration) augumented the sub‐hyperphagic effect to diazepam (0.5 mg/kg, sc). Thus, these findings suggest that hyperphagia to diazepam is mediated in part by both dopamine D‐1 and D‐2 receptors in non‐deprived rats.