Influence of novel and habituated testing conditions on cocaine sensitization

Female Swiss-Webster mice were treated daily for 10 days with cocaine (15 mg/kg i.p.) followed by 10 days with saline or ethanol (1.6 g/kg i.p.) or the reverse; following each injection in the experimental conditions locomotion was quantified in photocell cages. In animals given cocaine first, cocaine-induced locomotion was initially high and did not increase further with successive injections. In animals given prior saline or ethanol treatments, cocaine-induced locomotion was initially low but increased with successive cocaine treatments. There was no evidence of sensitization to the locomotor-stimulating effects of ethanol or of cross-sensitization between ethanol and cocaine. With respect to subsequent cocaine sensitization, the essential feature of prior saline or ethanol treatment appeared to be the handling and injection experience itself; a control group receiving prior saline injection in the home cage also showed a low level of cocaine-induced locomotion on the first day of cocaine testing but increasing locomotion with repeated cocaine testing. Thus, cocaine sensitization, rather than a progressive augmentation of motor function, may reflect a progressive reversal of the behavioral suppression caused by habituation to aspects of the testing situation or to some form of situational anxiety that precludes normal exploratory responses.