Withdrawal from oral cocaine in rate: ultrasonic vocalizations and tactile startle

While anxiety appears to characterize humans who administer high doses of cocaine or experience withdrawal from cocaine, it is difficult to capture this aspect of cocaine effects in animals. The present study investigated if acute or protracted withdrawal from prolonged low-dose cocaine that is self-administered via the oral route could be detected in tactile startle and vocal "distress" responses of rats. Adult, male Long-Evans rats had access to cocaine solution (0.1 mg/ml) either for 24 or 4 h/day using the two-bottle choice technique. The amount of solution consumed from each bottle was measured daily for 30 or 60 days. On days 1, 3, 7, 14, 21, 28 of withdrawal, startle and ultrasonic vocal responses (USV, 15-35 kHz) were measured in response to 18 air-puff stimuli (20 psi). Rats drank an average of 5-20 mg/kg per day of the cocaine solution. On average, about half of the daily liquid was consumed from the cocaine solution-containing bottle. USVs were emitted at significantly increased rates on day 3 of withdrawal from 30 or 60 days of cocaine drinking. Startle reactions were slightly, but non-significantly increased on day 1 of withdrawal. Comparable to withdrawal from ethanol, morphine, and diazepam treatments, withdrawal from oral self-administration of low to moderate doses of cocaine increases the rate of ultrasonic vocalizations while increasing minimally the amplitude of startle responses to low-intensity tactile stimuli. Nevertheless, no correlation between the total amount of cocaine self-administered or the duration of treatment with the intensity of the withdrawal manifestations could be detected.