BEHAVIOR GENETIC INVESTIGATION OF THE RELATIONSHIP BETWEEN SPONTANEOUS LOCOMOTOR-ACTIVITY AND THE ACQUISITION OF MORPHINE SELF-ADMINISTRATION BEHAVIOR

There is a significant degree of individual variability in response to drugs of abuse. A goal of behavior genetic studies has been to determ ine the extent to which observed heterogeneity in drug use can be attr ibuted to genetic and environmental factors and to identify the neurob iological factors involved in vulnerability. Recent hypotheses regardi ng the predictive value of spontaneous locomotor activity in the acqui sition of drug-reinforced behavior are amenable to testing using a beh avior genetics approach. Genetic differences in locomotor response to a novel environment were determined in naive and catheterized Lewis, F 344, NBR and ACI rats. Operant drug-reinforced behavior was examined i n a 23 h access paradigm in which each lever press by a rat produced a 1 mg/kg injection of morphine with a 30 s timeout period (FR 1:TO 30' '). Acquisition (7 days), extinction (6 days) and reacquisition (7 day s) of morphine self-administration behavior was investigated in all fo ur inbred strains. Large genetic differences in the rate of acquisitio n and extinction of morphine self-administration were found. Lewis rat s responded at high rates beginning in the first two days, whereas F34 4 rats initially responded at low rates and responding increased gradu ally over seven days. NBR and ACI rats responded at intermediate level s. When vehicle was substituted for drug there was a significant effec t of genotype on the rate of extinction; F344 and ACI increased respon ding to greater than 175% of drug-response levels, whereas the Lewis r esponse rate decreased gradually and NBR response rate decreased immed iately during the first several days. When drug was available again, r ates of reacquisition did not differ from original acquisition rates. Drug maintained significantly greater amounts of behavior than vehicle in the Lewis, F344 and NBR rats and was thus shown to serve as a posi tive reinforcer in these three strains under these conditions. There w as a significant genetic correlation among strains between drug intake during the first five days of acquisition and spontaneous locomotor r esponse to a novel environment in catheterized rats. Only the ACI rats showed a significant within-strain correlation. The positive relation ship between rate of acquisition of self-administration behavior and l ocomotor activity suggests that these two traits are influenced by com mon or closely linked genes. To this end, the neurobiological substrat es that mediate spontaneous locomotor behavior under these environment al conditions may act, in part, as a template for determining the neur obiological substrates that mediate the relative rate of acquisition o f morphine-taking behavior under these conditions.