State-dependent peculiarities of cocaine-induced behavioral sensitization and their possible reasons

To study determinants and possible reasons of cocaine-induced behavioral sensitization, locomotor effects of the drug (COC, 15 mg/kg, IP; 5 daily injections followed by a "challenge," four days later) and various stimuli associated (procedure of injection, placement in the test cage) and nonassociated (tail-pinch) with its administration were measured in rats under different experimental conditions. When COC was injected in quite conditions, two hours after animal habituation to the test cages, locomotor response to the first drug injection was only slightly higher compared to one of saline and these responses were relatively stable following repeated treatment (no sensitization). An enhanced locomotor response to the procedure of injection (needle prick) without changes in responsivity to other stimuli used were found in these COC-treated rats. When COC was injected in activated conditions (animal placement in test cages), locomotor response to the first drug administration was significantly higher compared to one of saline and COC used in the quiet state and it was enhanced following repeated treatment (sensitization). More intense locomotion associated with placement in test cages without any changes in responses to other stimuli was found in rats after this procedure of treatment. Thus, locomotor effects of COC and dynamics of its changes following repeated treatment depend upon the organism's functional state accompanying the drug's effect. Reinforcing action of COC determining development of interinfluence of its effects and ones triggered by environmental variables (learning based on conditioning) is considered as a proposed initial cause and a main mechanism both for enhanced reactivity to cocaine administered under conditions of its previous use and to various environmental events associated with previous cocaine effects.