Cocaine: excitatory effects on sensorimotor reactivity measured with acoustic startle

Cocaine (2.5-10 mg/kg) caused a dose-related increase in the amplitude of the acoustic startle reflex in rats. In contrast, procaine (5-40 mg/kg) caused a dose-related decrease in startle, indicating that the effects of cocaine could not be ascribed to its local anesthetic effects. Cocaine's excitatory effects were blocked by pretreatment with haloperidol (0.5 mg/kg) but not by cyproheptadine or prazosin. The excitatory effects of cocaine (10 mg/kg) were markedly attenuated by pretreatment with reserpine (5 mg/kg 24 and 18 h earlier) but not by alpha-methyl-p-tyrosine (100 mg/kg 1 h earlier). In contrast, comparably sized excitatory effects of d-amphetamine were blocked by alpha-methyl-p-tyrosine and greatly enhanced by pretreatment with reserpine. Neither pretreatment blocked excitatory effects of apomorphine on startle. The data indicate that cocaine increases startle by acting through reserpine-sensitive pools of dopamine and provide further support for the conclusion that acoustic startle is enhanced by activation of dopamine receptors.