Ventral tegmental area region governs GABAB receptor modulation of ethanol-stimulated activity in mice
Section snippets
Animals
Originating from the genetically heterogeneous, HS/ibg mouse stock, FAST-1 and -2, and SLOW-1 and -2 mice, were independently produced by selective breeding for high and low sensitivity to EtOH-induced locomotor stimulation, respectively (Crabbe et al., 1987, Phillips et al., 1991, Shen et al., 1995a, Shen et al., 1995b). Selection was terminated after 37 generations when no further response had been observed across several generations (Phillips et al., 2002). These lines are now maintained at
Locomotor activity
Figure 2 shows time course data pooled on replicate and sex because these factors did not interact with the baclofen effect. When replicate effects are absent, we have argued that data for replicated selected lines most powerfully detect genetically correlated traits when combined over this factor (Crabbe et al., 1990). Inspection of the 60-min time course curves showed that the effects of i.c.v. baclofen waned after the first 30 min. When the time course data for the first 30 min of the
Discussion
Activation of GABAB receptors in the brain, in the absence of peripheral GABAB receptor activation, attenuated EtOH-induced locomotor stimulation. I.c.v. administration of the GABAB receptor agonist, baclofen, produced results almost indistinguishable from those seen after systemic baclofen (Shen et al., 1998): complete attenuation of the EtOH stimulant response. Anterior intra-VTA microinjection of baclofen also significantly attenuated or blocked EtOH’s locomotor stimulant effects in FAST
Acknowledgements
The authors thank Drs. Charlie Meshul, Amy Eshleman, and Aaron Janowsky for graciously providing expertise, assistance, and the use of laboratory space and supplies in support of the i.c.v. injection and autoradiography experiments. The authors also thank Janet Dorow and Carrie McKinnon for invaluable technical assistance. These experiments were supported by NIAAA grants F31 AA05577 and P50 AA10760, NIDA grant T32 DA07262, and the Department of Veterans Affairs.
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