Long-term haloperidol-treatment of mice: a change in beta-adrenergic receptor responsiveness.

Mice administered haloperidol 3 mg/kg/day in their drinking water for 21 days were tested for their locomotor responsiveness to saline or acid vehicle, dl-, l- or d-propranolol, metoprolol, butoxamine or practolol. Haloperidol-treated animals administered saline or acid-vehicle were, in five of six experiments, more active than animals withdrawn from vehicle-treatment. Haloperidol- and vehicle-treated animals responded differently to the non-selective beta-adrenoreceptor antagonists (dl-propranolol and l-propranolol) and selective beta1-adrenoreceptor antagonists (practolol and metoprolol), but not to a selective beta2-adrenoreceptor antagonist (butoxamine). With dl-propranolol (4 mg/kg) the locomotor activity of haloperidol-treated animals was significantly (0.01 less than P less than 0.02) greater than that of the vehicle-treated animals. Similar effects in the same direction were seen with l-propranolol (1 mg/kg, 0.005 less than P less than 0.01), practolol (10 and 100 mg/kg, 0.025 less than P less than 0.05 and 0.01 less than P less than 0.025 respectively) and metoprolol 8 mg/kg, 0.005 less than P less than 0.01). The d-isomer of propranolol which is about 50 times less active as a beta-adrenoreceptor antagonist than the l-isomer, although having equal membrane stabilizing effects, did not differentially affect haloperidol- or vehicle-treated groups. The results suggest that there has been a change in beta 1-adrenoreceptor responsiveness in animals withdrawn from long-term haloperidol treatment.