Long-term haloperidol-treatment of mice: A change in β-adrenergic receptor responsiveness

Summary

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- ord-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animals administered saline or acid-vehicle were, in five of six experiments, more active than animals withdrawn from vehicletreatment. Haloperidol- and vehicle-treated animals responded differently to the non-selectiveβ-adrenoreceptor antagonists (dl-propranolol andl-propranolol) and selectiveβ ₁-adrenoreceptor antagonists (practolol and metoprolol), but not to a selectiveβ ₂-adrenoreceptor antagonist (butoxamine). Withdl-propranolol (4 mg/kg) the locomotor activity of halo-peridol-treated animals was significantly (0.01<P<0.02) greater than that of the vehicle-treated animals. Similar effects in the same direction were seen withl-propranolol (1 mg/kg, 0.005<P<0.01), practolol (10 and 100 mg/kg, 0.025<P<0.05 and 0.01<P<0.025 respectively) and metoprolol (8 mg/kg, 0.005<P<0.01). Thed-isomer of propranolol which is about 50 times less active as aβ-adrenoreceptor antagonist than thel-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 The results suggest that there has been a change inβ ₁-adrenoreceptor responsiveness in animals withdrawn from long-term haloperidol treatment.