Blocking alpha2A adrenoceptors, but not dopamine receptors, augments bupropion-induced hypophagia in rats.

OBJECTIVE

Anti-obesity drugs have adverse effects which limit their use, creating a need for novel anti-obesity compounds. We studied effects of dopamine (DA) and norepinephrine (NE) reuptake inhibitor bupropion (BUP), alone and after blocking α1- or α2-adrenoceptors (AR), D1/5, D2/3, or D4 receptors, to determine which receptors act downstream of BUP.

DESIGN AND METHODS

Effects on caloric intake, meal patterning and locomotion were assessed, using an automated weighing system and telemetry in male rats with 18-h access to Western Human style diet.

RESULTS

BUP (30 mg/kg) induced hypophagia by reducing meal size and postponing meal initiation. WB4101 (α1-AR; 2 mg/kg) and imiloxan (α2B-AR; 5 mg/kg) attenuated BUP's effect on meal size, while WB4101 and BRL 44408 (α2A/D-AR; 2 mg/kg) counteracted effect on meal initiation. Atipamezole (α2-AR; 1 mg/kg) and imiloxan further postponed initiation of meals. SKF 83566 (D1/5; 0.3 mg/kg), raclopride (D2/3; 0.5 mg/kg) and to a lesser extent FAUC 213 (D4; 0.5 mg/kg), attenuated BUP-induced hypophagia. BUP stimulated locomotion, which was blocked by all antagonists, except FAUC 213 or BRL 44408.

CONCLUSIONS

Alpha1-, α2A/D- and α2B-ARs, and DA receptors underlie BUP's effects on size and initiation of meals, while blocking pre-synaptic α2-ARs enhanced BUP-induced hypophagia. An inverse agonist of (pre-synaptic) α2A-ARs could enhance BUP-induced anorexia and treat eating disorders and obesity.