Multiple exposures to ethanol facilitate intravenous self-administration of ethanol by rats

Abstract

In experiment 1, male hooded rats (N=11) were implanted with jugular cannulas, and housed in sound attenuated operant chambers 24 hr/day. The rats were exposed to periodic cycles of forced ethanol infusions (30% v/v, 9–16 g/kg/day over 4–6 days for each cycle). Following each cycle, forced infusions were discontinued, but the rats were allowed access to a lever for self-administration of ethanol on a fixed ratio 1 schedule (FR1). Each lever press infused 0.2 ml of ethanol (20% v/v). The rats were maintained on self-administration for at least 24 hr. If a rat did not develop self-administration behavior (SAB) within 24 hr, the next forced cycle of ethanol exposure was initiated. Eight of the 11 rats developed SAB after a mean of 5.25 cycles of exposure to ethanol, and were then tested for a mean of 15 days on self-administration under FR1, FR2, and FR3 schedules of reinforcement. All rats were tested on FR1 and self-administered a mean of 10.43 g ethanol/kg/day over a mean of 10.75 days. Four rats were subsequently tested on FR2 and FR3 and increased lever presses in order to maintain daily ethanol intake comparable to FR1. Following self-administration testing, the rats were placed on withdrawal and exhibited mild to severe withdrawal symptoms, suggesting that SAB maintained physical dependence. In Experiment 2, rats (N=6/group) were allowed to self-infuse either saline or ethanol (20% v/v). These rats had no prior exposure to either saline or ethanol, and forced infusions were never administered. The rats remained in their operant chambers for 21 days under FR1 contingencies. Each lever press led to a 0.2 ml infusion. None of the rats developed SAB, but the saline controls made more lever presses than the ethanol rats ( p<0.01). These results suggest that the ethanol parameters yielding SAB in Experiment 1 are aversive to ethanol naive rats.