Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice

Abstract

The present study compared cocaine-induced hyperlocomotion and cocaine i.v. self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after i.p. cocaine injection (0-60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocaine i.v. self-administration experiment, they were compared for their ability to acquire and maintain cocaine self-administration in operant chambers with levers as the manipulanda. Animals were first trained to respond for food as a reinforcer (condensed milk solution); they were then submitted to surgical i.v. insertion of an in-dwelling catheter, and required to respond for i.v. cocaine (0.25-4.0 mg/kg per injection) as a reinforcer. DBA/2J mice showed significantly higher maximal cocaine-induced hyperlocomotion, more rapid acquisition of cocaine self-administration, and significantly lower rates of cocaine self-administration. Cocaine concentration in the brains of DBA/2J and C57BL/6J mice failed to differ following i.p. injection, suggesting that distribution factors were not involved in the differential responses to cocaine. Although not conclusive, this pattern of effects may suggest that cocaine has greater reinforcing efficacy in DBA/2J mice, confirming genetic make-up as a determinant factor in cocaine taking behavior.

Anxiogenic-Like Effects Limit Rewarding Effects of Cocaine in BALB/cByJ Mice

“…Specifically, individuals with low trait anxiety may need more stimulation to achieve the same rewarding experience than individuals with high trait anxiety (Figure 10). Accordingly, evidence from several previous studies show that nonemotional inbred strains such as C57BL/6 readily self-administer high doses of cocaine (Carney et al 1991;Grahame et al 1995;Rocha et al 1998), and we have shown qualitative and quantitative differences in self-administration between BALB/cByJ and C57BL/6 x SJL hybrid mice (Deroche et al 1997).…”

“…The first observation resulting from the present experiment is that BALB/cByJ mice exhibited intravenous cocaine self-administration behavior when using a low dose known to be ineffective in several other strains (Carney et al 1991;Grahame et al 1995;Deroche et al 1997;Rocha et al 1998). The use of a habituation session allowing the mice to explore the apparatus freely before cocaine was made available may have favored the expression of this behavior.…”

“…These behaviors are also expressed differentially in inbred strains of mice making these mice a potentially important model for further examining the relationship between behavioral traits, their underlying biological basis, and drug-seeking behavior (Crabbe et al 1994). Of particular interest in this context is the difficulty of demonstrating intravenous cocaine self-administration in BALB/cByJ mice (Deroche et al 1997;Roberts et al 1997;Yu et al 1997), using doses known to maintain self-administration in C57BL/6 or several other strains (Carney et al 1991;Grahame et al 1995;Deroche et al 1997;Rocha et al 1998). This observation cannot be accounted for by pharmacokinetic differences (Ruth et al 1988), capacity to learn operant tasks (Cazala 1976;Deroche et al 1997;Heyser et al 1997), or sensitivity to disruption of operant responding by acute cocaine .…”

Repeated Ethanol Intoxication Induces Behavioral Sensitization in the Absence of a Sensitized Accumbens Dopamine Response in C57BL/6J and DBA/2J Mice

“…This association, however, may depend on the drug tested. For example, although several laboratories have shown that DBA/2J mice show enhanced cocaine-evoked locomotion compared to C57BL/6J (Rocha et al, 1998;Phillips et al, 1998), a microdialysis study found no difference in the magnitude of cocaine-evoked DA levels in the nucleus accumbens between these two mouse strains (He and Shippenberg, 2000). The results obtained on ETOH-evoked DA levels in the nucleus accumbens are supported by a previous in vitro study in which ETOH-stimulated DA cell firing in ventral tegmental area slices of DBA/2J mice was similar to that in C57BL/6J mice (Brodie and Appel, 2000), at least at the same ETOH concentrations used in the present study.…”

Role of the Dopamine Transporter in the Differential Cocaine-Induced Locomotor Activation of Inbred Long-Sleep and Short-Sleep Mice

“…Pharmacogenetic studies in C57 and DBA mice support the above-mentioned hypothesis as these mouse lines exhibit parallel differential sensitivity to the locomotorstimulant effects of both ethanol and cocaine, with C57 mice exhibiting less locomotion to both drugs (Rocha et al, 1998;Tolliver and Carney, 1995;Womer et al, 1994). However, this is not the case with all mouse lines.…”