[Delta]FosB protein and its role in the nucleus accumbens - an important factor in addiction, stress and response to natural rewards and psychoactive drugs

Abstract

ΔFosB is a transcription factor and a member of Fos family proteins. It has been identified to be a factor both in physiological reward-seeking behavior and in development of addiction. Its expression in the nucleus accumbens in response to chronic stimulation of the reward system triggers neuroplasticity in this system. Although ΔFosB expression increases in response to many different stimuli, its exact effects differ depending strictly on the brain region and type of neurons in which the expression takes place. Among stimuli known to induce ΔFosB expression are exercise, sexual activity, calorie-rich foods and stress, but also psychoactive drugs (stimulants, opioids, alcohol, tobacco, propofol), electroconvulsive therapy, antipsychotics of both generations and antidepressants. Increased ΔFosB levels in nucleus accumbens medium spiny neurons with dominant D1 receptor expression have been associated in mice with stress resilience, but also with increased susceptibility to developing an addiction and higher frequency of risky behaviors. Increased ΔFosB expression in the same neuron type, but with dominant D2 receptor has been observed after rearing mice in a mentally enriching environment and following high-sucrose drink consumption. Decreased ΔFosB levels have been demonstrated post mortem in the nucleus accumbens in patients suffering from depression and in the prefrontal cortex after chronic antipsychotic drug administration. The ΔFosB half-life is exceptionally long - this protein has been shown to last even for several months after cessation of the stimuli - and it accumulates following chronic stimulation. Both its abnormal stability and neuroplasticity-inducing properties could explain the chronic course of addiction.