Stress and Rodent Models of Drug Addiction: Role of VTA-Accumbens-PFC-Amygdala Circuit

Abstract

Stress can trigger, intensify, and prolong drug consumption, as well as reinstate previously extinguished drug-taking behavior by directly impacting a neural circuit often referred to as a reward pathways. Animal models of drug abuse have been used to understand these neural circuits mediating stress-induced drug intake and relapse through examination of cellular and subcellular molecular mechanisms. Several types of intermittent stressors have been shown to induce cross-sensitization to psychomotor stimulants, enhance conditioned place preference under most conditions, increase self-administration of cocaine and amphetamine and induce reinstatement of heroin and cocaine seeking via activation of the mesocorticolimbic dopamine system.

Figure 1

The effect of repeated (a) amphetamine (1.0 mg/kg, i.p.) and (b) social defeat stress on horizontal locomotor behavior following amphetamine challenge (1.0 or 1.5 mg/kg, i.p., respectively) on day 20, 10 days after the last defeat experience. Locomotor activity 30 min after injection is shown. *P<0.05 compared with no stress or saline controls. From Yap et al. (2005).

Figure 2

The effect of 4 brief, intermittent social defeat episodes on hourly cocaine self-administration during a 24-hour cocaine binge (0.3 mg/kg/infusion). Circadian-like cocaine self-administration behavior was maintained in control rats (open circles), whereas stressed rats (filled circles) self-administered cocaine intensely for 24 hours, effectively abolishing the circadian pattern of intake (p < 0.01). From Covington et al. (2005).