6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence cocaine-induced place conditioning

This study investigated the involvement of medial prefrontal cortex (mPFC) dopamine in cocaine place conditioning using a totally balanced place conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These lesions significantly depleted dopamine (−83%) and norepinephrine (−70%) in the mPFC but there were no significant reduction in either the nucleus accumbens or in the caudate-putamen compared with sham-operated controls. Furthermore, serotonin levels were not affected in any of the brain regions investigated. These lesions failed to attenuate place conditioning induced by the intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham lesioned controls. In addition, there were no significant differences in spontaneous locomotor activity between the two groups during the preconditioning phase or the test phase. These results suggest that 6-OHDA lesions which produced profound depletions of dopamine and norepinephrine in the mPFC did not alter the rewarding efficacy of cocaine as measured by the place conditioning paradigm.