Psychological dependence develops through consistent and frequent exposure to a stimulus. After sufficient exposure to a stimulus capable of inducing psychological dependence (e.g., drug use), an adaptive state develops that results in the onset of withdrawal symptoms that negatively affect psychological function upon cessation of exposure. Behaviors such as excessive exercise can lead to exercise dependence in both amateur and professional athletes, where cognitive withdrawal symptoms—such as anxiety and irritability—arise during periods of abstinence and often correlate with the duration of abstinence. The process responsible for the induction of psychological dependence is a
negative feedback mechanism that involves neuronal-counter adaptation, leading to tolerance to the desirable effects of certain drugs or stimuli and a subsequent withdrawal syndrome upon abrupt cessation of exposure. In addition to CREB, it is hypothesized that stress mechanisms play a role in dependence. Koob and Kreek have hypothesized that during drug use, activates the
hypothalamic–pituitary–adrenal axis (HPA axis) and other stress systems in the
extended amygdala. This activation influences the dysregulated emotional state associated with psychological dependence. They found that as drug use escalates, so does the presence of CRF in human
cerebrospinal fluid. In rat models, the separate use of CRF inhibitors and
CRF receptor antagonists both decreased
self-administration of the drug of study. Other studies in this review showed dysregulation of other neuropeptides that affect the HPA axis, including
enkephalin which is an endogenous
opioid peptide that regulates pain. It also appears that
μ-opioid receptors, which enkephalin acts upon, is influential in the
reward system and can regulate the expression of
stress hormones. Increased expression of AMPA receptors in nucleus accumbens MSNs is a potential mechanism of aversion produced by drug withdrawal. == Methods for reducing dependence ==