Cocaine effects on mouse incentive-learning and human addiction are linked to alpha 2 subunit-containing GABA(A) receptors

Because GABA(A) receptors containing alpha 2 subunits are highly represented in areas of the brain, such as nucleus accumbens (NAcc), frontal cortex, and amygdala, regions intimately involved in signaling motivation and reward, we hypothesized that manipulations of this receptor subtype would influence processing of rewards. Voltage-clamp recordings from NAcc medium spiny neurons of mice with alpha 2 gene deletion showed reduced synaptic GABA(A) receptor-mediated responses. Behaviorally, the deletion abolished cocaine`s ability to potentiate behaviors conditioned to rewards (conditioned reinforcement), and to support behavioral sensitization. In mice with a point mutation in the benzodiazepine binding pocket of alpha 2-GABA(A) receptors (alpha 2H101R), GABAergic neurotransmission in medium spiny neurons was identical to that of WT (i.e., the mutation was silent), but importantly, receptor function was now facilitated by the atypical benzodiazepine Ro 15-4513 (ethyl 8-amido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5-a] [1,4] benzodiazepine-3-carboxylate). In alpha 2H101R, but not WT mice, Ro 15-4513 administered directly into the NAcc-stimulated locomotor activity, and when given systemically and repeatedly, induced behavioral sensitization. These data indicate that activation of alpha 2-GABA(A) receptors (most likely in NAcc) is both necessary and sufficient for behavioral sensitization. Consistent with a role of these receptors in addiction, we found specific markers and haplotypes of the GABRA2 gene to be associated with human cocaine addiction.

Home range, movements and diurnal roosts of the endangered thin-spined porcupine, Chaetomys subspinosus (Rodentia: Erethizontidae), in the Brazilian Atlantic Forest

Chaetomys subspinosus is the sole species within the Chaetomyinae subfamily of Caviomorph rodents. This poorly studied porcupine is restricted to the Atlantic Forest in eastern Brazil, where deforestation and habitat fragmentation threaten its survival. Data on the ranging and roosting behavior of C. subspinosus is fairly scarce as it is difficult to observe these behaviors in nature and, consequently, it is very rarely detected during field surveys. We monitored the home ranges of three radio-tagged females over the course of 1 year (2005-2006) and collected data on several aspects of their natural history including movement patterns and the use of diurnal roosts and latrines. The animals were monitored at Parque Estadual Paulo Cesar Vinha, a nature reserve dominated by restinga forests, a subtype of Atlantic Forest occurring on sandy soil. The estimated home range varied little between individuals and was relatively small (mean = 2.14 ha/individual and 1.09 ha/individual using minimum convex polygon and kernel methods, respectively). The animals travelled an average of 147 m/night (range: 21-324 m/night) between two consecutive day roosts. The day roosts were mostly located on vine and liana tangles in the canopy which also aid in connecting the canopy to adjacent trees or the forest floor. Latrines were mostly located near the ground in places heavily protected by spiny bromeliads or by other tangled vegetation. Our data suggests that C. subspinosus has the smallest range among all Neotropical Erethizontids which is likely due to its small size and strictly folivorous diet. Our data also helps explain why C. subspinosus is so difficult to observe in nature: researchers should focus on arboreal masses of tangled vegetation where individuals will normally rest during the day. (C) 2011 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.