Ethanol modulates cocaine-induced behavioral change in inbred mice.

We recently conducted a study of the behavioral effects of combined cocaine and ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2) were tested in an automated activity monitor on 2 consecutive days. On day 1, all animals received an IP injection of sterile saline and were placed into the activity monitor for 30 min. Behaviors measured were total distance traveled, stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again for 15 min following injection of one of the following: saline, 10% v/v ethanol at 2.0 g kg(-1) or 2.0 g kg(-1) ethanol plus 5, 15, or 30 mg kg(-1) cocaine. Cocaine alone at the same doses was injected into separate groups of animals. For the B6 strain, the overall effect of ethanol was to reduce cocaine-induced locomotor stimulation; no consistent effect of ethanol on cocaine-induced locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in both strains and sexes was partially reversed by ethanol. Ethanol also partially reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice, cocaine-increased wall seeking tended to be reversed by coadministration of ethanol, whereas no consistent pattern was observed in the D2s. Results from this study suggest that the several measures affected by cocaine (locomotor activity, stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by concurrent treatment with ethanol. Furthermore, our results point to genetic-based differences in ethanol's effects on cocaine-related behaviors. We address the implications for combined ethanol and cocaine use in humans.

Sex and strain influence the effect of ethanol on central monoamines.

OBJECTIVE: We recently investigated the effects of EtOH on the mesolimbic dopamine and serotonin systems in male and female C57BL/6 (B6) and DBA/2J (D2) mice. METHOD: Male and female rodents from the B6 and D2 mouse strains (n = 11 per strain, sex and dose) were used in this study. Doses of EtOH (vs saline) administered were 1.0, 2.0 or 3.0 g/kg. RESULTS: Treatment with saline or EtOH produced both strain- and sex-dependent differences in patterns of monoamine response. For example, D2s exhibited significantly higher overall dopamine (DA) levels than did B6s in the frontal cortex (FC), nucleus accumbens (NA) and caudate-putamen (CP). In the FC, female D2 evinced elevated 5HIAA at 1.0 g/kg. In the NA, D2 females showed dose related increases in levels of DA up to 3.0 g/kg, whereas in the D2 males and in B6 males and females we observed no response. Also in the NA, B6 males showed increases in dihydroxyphenyacetic acid (DOPAC) at 1.0 and 3.0 g/kg. In the CP, B6 males showed higher DA levels than B6 females at the saline, and all EtOH doses. For serotoninergic activity in the CP as well as the NA, EtOH produced a distinctive triphasic response, with the 1.0 and 3.0 g/kg doses of EtOH producing higher levels than saline and 2.0 g/kg of 5HIAA in B6 males than in B6 females. CONCLUSIONS: Our findings indicate strain and sex differences in monoamine response to acute doses of ethanol, and further implicate (via changes in DOPAC) presynaptic mechanisms in the effects of ethanol on dopamine.