Withdrawal from IV cocaine "binges" in rats: ultrasonic distress calls and startle

Abstract

Human cocaine abusers report that they experience intense anxiety during withdrawal from chronic use or "binging". Because the symptoms of cocaine withdrawal are not easily observed, it has been difficult to develop an adequate animal model for cocaine withdrawal that detects anxiety-like behavior. The objective of the present study was to examine the effects of continuous access to i.v. self-administered cocaine on ultrasonic vocalizations (USVs) induced by startling tactile stimuli as a possible animal model for cocaine withdrawal. Five days after implantation of a jugular catheter, rats were placed into self-administration chambers with access to cocaine (0.25 mg/infusion). Once the animal had a stable response rate over 3 days, on a fixed schedule of reinforcement (FR5), they were given unlimited access to cocaine (0.25 mg/infusion) for 48 or 12 h. Subsequently, animals were exposed to 18 air puffs (20 or 10 psi) at 6, 24, 72 h, 7 and 14 days after the "binge". Rats that self-administered cocaine for 48 h and were subsequently startled with 20 psi stimuli increased the number of automatically recorded ultrasonic distress calls and showed an enhanced startle response at 6 h after the last cocaine infusion when compared to handled controls. Animals that self-administered cocaine for 48 h and were subsequently startled with 10 psi stimuli showed increased USVs and an enhanced startle reflex at both 6 and 24 h after the unlimited access. Animals that self-administered cocaine for 12 h also showed an increase in ultrasonic distress calls and enhanced startle responses to 10 psi tactile stimuli when compared to handled controls. USVs during cocaine withdrawal may be interpreted to reflect affective distress during the first 24 h after the last cocaine infusion of 12 or 48 of continuous access to drug.