The reduction of food intake in hungry rats induced by salbutamol (10 mg/kg/i.p.) was prevented by IPS 339 (5 mg/kg, i.p.) a selective β2 adrenergic antagonist, but not by metoprolol (10 mg/kg i.p.), a blocker of β1 adrenergic receptors. Similarly, bilateral injections of IPS 339 (32 μg/1 μl) but not metoprolol (80 μg/1 μl) in the perifornical hypothalamic area completely antagonized the anorectic effect of intraperitoneal salbutamol, suggesting an involvement of β2 adrenergic receptors in this brain area. Clenbuterol, a β2 adrenergic agonist which readily crosses the blood-brain barrier, was 10-100 times more potent than salbutamol in inhibiting feeding consumption of deprived rats when injected intraperitoneally and this effect was also selectively antagonized by pretreatment with IPS 339. Neither IPS 339 nor metoprolol injected in the perifornical hypothalamus significantly modified the anorectic effect of diethylpropion (5 mg/kg i.p.) whereas it was partially prevented by intraperifornical injection of 1-propranolol (52 μg/2 μl), a non-selective β antagonist, suggesting that both β1 and β2 adrenergic receptors in the hypothalamus contribute to the mechanism by which diethylpropion causes anorexia.
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