Circling behavior following systemic d-amphetamine administration: potential noradrenergic and dopaminergic involvement.

Systemic treatment with d-amphetamine produced a dose-dependent increase in the circling behavior of normal mice. Treatment with both alpha-methyl-p-tyrosine (alpha-MpT) and FLA-63 antagonized the amphetamine-induced circling behavior. Similarly, blockade of B-adrenergic receptors by propranolol and dopamine receptors by haloperidol reversed the circling response elicited by amphetamine. In contrast to alpha-MpT and haloperidol, however, neither FLA-63 nor propranolol attenuated the locomotor excitation engendered by amphetamine. Following repeated d-amphetamine injections the circling ordinarily induced by a single injection was abolished, whereas the locomotor effects of amphetamine remained unaltered. These findings are consistent with earlier work suggesting that tolerance may occur in those behaviors that involve a noradrenergic component.