Mechanisms of Increased Cocaine Self-Administration

MacEnski, Mitchell

Abstract

Cocaine abuse continues to be a major social and medical problem in the United States. With reports that there are 2 to 3 million chronic cocaine users, cocaine use is a continuing public health problem . Concurrent alcohol dependence occurs in 62 to 94% of chronic cocaine users. Information gained from comorbid cocaine and ethanol abuse. Self-administration of a cocaine and ethanol combination is of special importance. There are significant neurochemical, physiological, behavioral and treatment related interactions when cocaine and ethanol are concurrently administered. A key concern relevant to human drug abuse is to determine if concurrent cocaine and ethanol self- administration has greater abuse potential than either drug alone. Self-administration of single and polydrug combinations will be examined in four rhesus monkeys. Two methods have shown predictive utility in assessing abuse potential. In experiment 1, monkeys will have a choice among pairs of 0.4 mg/ml cocaine, 8% ethanol, vehicle and a combination of both drugs. In experiment 2, monkeys will respond for the same solutions listed above under conditions of within session increases in cost (i.e., progressive-ratio). Both of these procedures will rigorously test the hypothesis that the cocaine-ethanol combination has greater rewarding effects than the constituents or vehicle. Two, of several, mechanisms which may account for the interactions observed during concurrent cocaine and ethanol self- administration are 1) ethanol may """"""""mask"""""""" cocaine's taste leading to increased intake and 2) liver production of cocaethylene, a third psychoactive substance, may increase the overall reinforcing effect. Experiment 3 tests the hypothesis that preference for cocaine and ethanol is based on taste by substituting saccharin for ethanol and completing a choice procedure as in Experiment 1. In Experiment 4, monkeys will self-administer the drug combination and blood will be drawn so that cocaethylene plasma concentrations can be measured. This information is necessary to support the hypothesis that cocaethylene plays a role in cocaine-ethanol interactions. The well established methods provided are excellent vehicle by which to examine the clinically relevant hypothesis. An important aspect of this application is its direct focus on clinically pertinent issues of drug abuse.