In recent years, a complex picture has emerged concerning the nuclear transcription factor AFosB and its behavioral effects in drug addiction and reward. DeltaFosB is currently viewed as a possible molecular mediator of the long-term neural plasticity observed after chronic drug exposure (Nestler, 2001). DeltaFosB levels increase and remain elevated after chronic drug exposure (Nestler et al., 1999) and increases in AFosB sensitize a number of behavioral responses to the rewarding or positively reinforcing effects of drugs of abuse (Kelz et al., 1999;Colby et al., 2003). In addition, increases in AFosB have been shown to increase the rewarding value of natural rewards as well (Werme, et al., 2002;Olausson, et al., 2006). While the role of elevated AFosB has been examined in a number of behavioral aspects of drug addiction and, to a smaller extent, natural rewards, the devaluation of natural rewards by drugs of abuse has remained relatively unexplored. To this end, the current proposal will use adeno-associated viral mediated gene transfer to elevate AFosB specifically in the nucleus accumbens of C57BL/6 mice.
Specific Aim I will evaluate the effect of elevated AFosB on preference for natural rewards by evaluating two-bottle preference tests for a rewarding (saccharin), neutral (NaCI), and aversive (quinine) taste stimuli.
Specific Aim II will evaluate the effect of elevated AFosB in a model of drug-induced devaluation of natural rewards (reward comparison). Finally, Specific Aim III will test whether elevation of AFosB leads to increased 'impulsivity'to respond to a rewarding taste stimulus. Drug addiction often leads to decreased motivation for things that were once pleasurable before drug use such as friends, family, work, hobbies, and even health. This devaluation of naturally rewarding stimuli in the environment, in favor of the drug of abuse, leads to personal and public costs as the addict is no longer able to beneficially function in society. The present proposal seeks to further elucidate a possible molecular mediator of the neural plasticity that leads to this behavior.
| Freet, Christopher S; Alexander, Danielle N; Imperio, Caesar G et al. (2018) Heroin-induced suppression of saccharin intake in OPRM1 A118G mice. Brain Res Bull 138:73-79 |
| Freet, Christopher S; Arndt, Amanda; Grigson, Patricia S (2013) Compared with DBA/2J mice, C57BL/6J mice demonstrate greater preference for saccharin and less avoidance of a cocaine-paired saccharin cue. Behav Neurosci 127:474-84 |
| Freet, Christopher S; Steffen, Cathy; Nestler, Eric J et al. (2009) Overexpression of DeltaFosB is associated with attenuated cocaine-induced suppression of saccharin intake in mice. Behav Neurosci 123:397-407 |
