The effects of dose and access restrictions on the periodicity of cocaine self-administration in the rat.

Cocaine self-administration in rats was tested under various dose and frequency of access restrictions. In the continuous access condition, groups of rats were given continuous, unlimited access to one of three doses of cocaine (1.5, 0.5, and 0.2 mg/kg/infusion) for a duration of 10 days. In the discrete trials condition, a group of rats were given the opportunity to self-administer a single cocaine infusion (1.5 mg/kg) within a discrete, 10 min access trial. The rats received a continuous series of these trials for a duration of 7-10 days at one of three frequencies (1, 2 or 4 trials/h). Results suggest that when access is restricted to four access trials/h, or to a median dose range (0.5 mg/kg per infusion), rats will self-administer cocaine in a cyclical manner over extended, infradian periodicities without developing outward signs of ill health. This contrasts with previous studies where extended, unlimited access schedules have resulted in toxicity and overdose. It is suggested that dose and frequency of access restrictions may be employed in order to develop new animal models of cocaine self-administration which examine the factors underlying the reinitiation of extended periods of cocaine intake. Such models may be useful in testing interventions with the potential to disrupt cyclical patterns of cocaine self-administration.