Cocaine self-administration "binges": transition from behavioral and autonomic regulation toward homeostatic...

An essential feature of cocaine addiction is the breakdown to control or regulate drug intake.

The present studies aimed to examine the transition from regulated intravenous cocaine reinforcement to a more unpredictable, chaotic pattern of cocaine self-administration in rats that were given continuous access to the drug. Autonomic activity was continuously monitored via biotelemetry senders for heart-rate and core temperature before, during and after the cocaine "binges", in an attempt to characterize the breakdown of homeostatic regulation.

After Long-Evans rats were fitted with intravenous catheters and intraperitoneal telemetry senders, they acquired cocaine self-administration with each fifth lever press being reinforced by a 0.25 mg cocaine infusion. Rats self-administered 15 cocaine infusions daily at stable rates for ca. 2-3 weeks, when continuous access periods ("binges") of 26 and 72 h were scheduled, with a 3-week cocaine-free period between and following the two "binges".

A distinctive pattern of cocaine self-administration emerged during the "binges" that consisted of (1) an initial loading phase, (2) stable, predictable inter-infusion intervals for up to 8-10 h, termed "regulatory phase", (3) increased variability in inter-fusion intervals, mostly beginning at 22-24 h of continuous access. During the first half of the 72-h "binge", the autonomic activities remained elevated, showed a greatly constrained variability, and the characteristic circadian rhythmicity was substantially decreased. The average cocaine intake (6.8+/-0.5 mg/kg per hour) during the "regulatory" phase did not change during the subsequent phases. Following the 72-h "binge", the amplitude of autonomic circadian rhythms remained attenuated for more than 2 weeks. In a separate set of animals, the dose effect of inter-infusion intervals following the self-administered infusion was similar during a variable dose protocol, scheduled in an early and a late phase of a 30-h long "binge".

The homeostatic dysregulation during the "binge" as evidenced by the diminished capacity of autonomic functions to vary is accompanied by emerging irregularities in the pattern of cocaine self-administration.