The Implication of the Corticotropin Releasing Factor in Nicotine Dependence and Significance for Pharmacotherapy in Smoking Cessation

it (Skinner and Aubin, 2010). Drug use initially causes an acute release of dopamine from the nucleus accumbens (NAc) and initiates the release of opioids, producing a rewarding affective state (Koob and Volkow, 2010). However, this drug-induced reward is opposed by processes that reduce drug effects and attempt the return of hedonic states to homeostasis (Koob and Volkow, 2009). This is done through the activation of the brain’s stress system, the corticotropin releasing factor (CRF) system that then signals to the extended amygdala and hippocampus to elicit a stress response (Koob and Volkow, 2009). Thus, repeated use and activation of the opponent b-processes leads to a reduction in drug effects resulting in the development of tolerance and withdrawal symptoms in abstinence (Skinner and Aubin, 2010). Taken together, the compulsive nature of addiction can thus be viewed as a cycle of increasing dysregulation of brain reward and anti-reward mechanisms that results in a shifting hedonic baseline due to b-processes failing to return to normal homeostatic range (Garavan et al., 2000). In other words, chronic drug use leads to the elevation of reward thresholds that do not return to baseline during abstinence, leading to marked dysphoria and anhedonia, i.e. negative affect and an inability to experience pleasure (Garavan et al., 2000). Current research has shifted its focus to investigate how avoiding those dysphoric feelings produced in abstinence acts as a powerful motivator for continuous use through negative reinforcement. Thus, a paradox emerges in developing effective drug rehabilitation treatments as abstinence is both the ultimate goal and one of the reasons behind compulsive use. The development of an effective treatment is particularly important for smoking, since cigarette smoking constitutes a major health risk factor and is the leading cause of preventable deaths The Implication of the Corticotropin Releasing Factor in Nicotine Dependence and Significance for Pharmacotherapy in Smoking Cessation