COCAINE SENSITIVITY IN ROMAN HIGH AND LOW-AVOIDANCE RATS IS MODULATEDBY SEX AND GONADAL HORMONE STATUS

Repeated exposure to stressful stimuli or psychostimulants increases s ensitivity to the motoric effects of these drugs, i.e. behavioral sens itization. The objective of the: present experiment was to determine t he interaction between factors that modulate psychostimulant sensitivi ty, i.e. sex and circulating gonadal hormone levels, in rats with a ge netically distinct locomotor response to novelty: Roman Low Avoidance rats (F:LA) freeze while Roman High Avoidance rats (RHA) remain motori cally active. Ninety-six male and female RHA and RLA. rats were gonade ctomized (GDX) just after weaning or as adults, or left gonadally inta ct. Each rat received a total of 9 injections of cocaine hydrocholorid e (10 mg/kg, IP), at 3-4-day intervals for 5 weeks. Locomotor activity was measured after each injection, and stereotypies were rated 1 x /w eek. Open field behavior (10 min) and plasma corticosterone were measu red 2 weeks after the final injection. Overall, the RHA line was more sensitive to (1) cocaine's stereotypic effects, and (2) the influence of ovarian hormones on the cocaine's acute and sensitizing effects on locomotor activity. Therefore, genetic background not only determines cocaine sensitivity, but also the influence of gonadal hormones on loc omotor activity. These interactions are relevant when considering the genetic contribution to abuse liability.