Absence of reinforcement with low dose intravenous ethanol self-administration in rats.

Male hooded rats were implanted with intravenous cannulas and housed in operant chambers supplied with 2 levers and enclosed in sound-attenuating cubicles. In Experiment 1, seven rats received a 1.0 mg/kg infusion of ethanol for each press on the previously determined non-preferred lever. The other lever served to count "activity lever presses." An additional 7 rats served as controls and were treated identically except that each press on the non-preferred lever led to an infusion of saline, isovolumetric to the ethanol infused in the experimental subjects. The rats were tested under these conditions of continuous reinforcement for 9 days. Throughout this period, self-infusions and "activity lever presses" did not differ between the groups, suggesting that ethanol was not reinforcing at a dose of 1.0 mg/kg. These results were replicated, and extended to other low doses of ethanol in Experiment 2. Here, we employed a design where depression of either lever, under conditions of continuous reinforcement, led to the infusion of a solution. Fifteen rats were randomly assigned to one of three groups (5 rats/group). In one group, depression of the previously determined non-preferred lever led to an infusion of 16.0 mg/kg of ethanol, while depression of the other lever led to an infusion of isocaloric glucose. For the other two groups, depression of the non-preferred level led to an infusion of 4.0 and 1.0 mg/kg ethanol respectively, and depression of the other lever led to a glucose infusion. The animals were tested for 9 days, and in each case, ethanol self-infusions did not differ significantly from glucose self-infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of two intravenous infusion schedules for inducing physical dependence upon ethanol in rat.

Male hooded rats were implanted with intravenous (IV) cannulas and housed in operant chambers. The effectiveness of two infusion schedules for producing physical dependence upon ethanol was assessed. Twenty-three rats (12 ethanol, 11 control) were tested under a 4 hr interinfusion schedule (one infusion every 4 hr, around the clock), and 29 rats (15 ethanol, 14 control) were tested under a 2 hr interinfusion schedule. During the dependence induction phase, which lasted for 6 days, the experimental rats received ethanol (30% v/v) at an average daily dose which ranged from 8.4-11.8 g/kg, and the dose administered per infusion was adjusted according to the degree of intoxication of each animal. The pair-fed control subjects received infusions of isocaloric control solutions (either 29% v/v propylene glycol or 31% v/v glycerol). Following the dependence induction phase, ethanol was withdrawn, and withdrawal symptoms were assessed. Blood ethanol levels (BEL) and signs of intoxication were determined through all phases of the experiment. During the dependence induction phase, mortality was close to zero, and weight loss was held to about 10%. Tolerance to ethanol developed in all experimental rats. During the withdrawal period, all ethanol rats developed clear withdrawal symptoms, while control subjects did not. Ethanol elimination rates ranged between 45-50 mg/dl/hr and withdrawal symptoms began when BEL fell below 200 mg/dl, and were severe when BEL approached zero. The 2 hr schedule proved superior to the 4 hr schedule in that it led to greater stability of BEL during dependence induction, and a tendency for the withdrawal reaction to be more severe.(ABSTRACT TRUNCATED AT 250 WORDS)