Previous findings have shown that a single restraint induce sensitization to the stimulating properties of d-amphetamine (AMPH), as measured by locomotor activity. The mesolimbic system innervating the nucleus accumbens (NAC) is implicated in the development and/or expression of sensitization. Different functions have been attributed to the dopamine (DA) in NAC core and shell activated by drugs and/or stress. In addition, many reports have pointed out a dopaminergic-glutamatergic interaction in the development of behavioral sensitization. Our main goals were: 1) to study the long term influence of a single restraint stress on AMPH-induced DA release by microdialysis from NAC core and shell and caudate putamen (CPu), eight days following restraint stress, 2) the involvement of NMDA receptors in the restraint stress-induced sensitization. Wistar male rats (250-320 g) were implanted stereotaxically under anesthesia with guide cannula. After two days, MK-801 (0.1 mg/kg i.p.) or vehicle were administered 30 min before restraint stress (2 h). Control animals received vehicle or MK-801 and returned to their home cages. Following eight days of restraint stress and/or MK-801, we evaluated the effect of AMPH (0.5 mg/kg i.p.) on DA release from NAC at both subdivisions, core and shell, and CPu by microdialysis during 3 hours. It was found that AMPH induced a significant higher increase only in DA release from NAC core in the restraint group, compared to that observed in the no restraint group. MK-801 blocked the restraint stress-induced effects of drug on DA release from NAC core. These findings showed a long term restraint-induced sensitization to AMPH on DA release from NAC core, and an involvement of NMDA receptors on it. These results support the hypothesis that common mechanisms between drugs and stress underlie their long term effects at the dopaminergic transmission in NAC core. Specifically, a glutamate-dopamine link is underlying the long term restraint stress-induced sensitization to stimulating properties of AMPH at NAC core.
