Sensitization to amphetamine and tolerance to cocaine and phencyclidine stimulation in mice

Abstract

Amphetamine (1.0–7.0 mg/kg), cocaine (5.0–40.0 mg/kg) and phencyclidine (1.0–7.0 mg/kg) increased acoustic startle responding in mice. These drugs, however, had varying effects on habituation of the startle response after repeated exposure to the auditory stimulus. The primary effect of phencyclidine was to disrupt the habituation process, whereas increased startle responding after cocaine developed without modification of the habituation curve. Amphetamine facilitated acoustic startle at all doses, and after administration of 3.0 mg/kg a significant response sensitization as a function of repeated stimulus presentation was evident. Consistent with previous reports the excitatory effects of cocaine and amphetamine on acoustic startle were blocked by pretreatment with haloperidol. Haloperidol, which decreased startle responding, attenuated the facilitating effects of PCP on acoustic startle as well. Chronic exposure to amphetamine, cocaine and phencyclidine had differential effects on startle responding. The facilitating effects of amphetamine on startle were further enhanced after long-term exposure to the drug and the sensitizing effect of repeated amphetamine exposure was observed only when animals were tested with amphetamine. In contrast, tolerance developed after chronic exposure to both cocaine and phencyclidine, and the response attenuation was evident when animals were tested for acoustic startle after cocaine, amphetamine and phencyclidine.