Anatomical and pharmacological specificity of the rewarding effect elicited by microinjections of morphine into the nucleus accumbens of mice

Rationale: The involvement of nucleus accumbens (NAc) in initiating opiate- induced reward has been difficult to demonstrate in rats, and has not been studied in mice. Objectives: To determine whether a reward-sensitive strain of mice (BALB/c) would self-administer morphine directly into the NAc or s ub-regions of the dorsal striatum. Methods: BALB/c mice were unilaterally i mplanted with a guide-cannula above either the NAc, the anterior caudate pu tamen, or the posterior caudate putamen. On each experimental day, a stainl ess-steel injection cannula was inserted into the guide cannula to test the capacity for morphine self-administration (6.5 pmol or 65 pmol/50 nl) usin g a spatial discrimination task in a Y maze. Results: Only the ventro-media l NAc group discriminated between the arm enabling a microinjection of morp hine and the neutral arm. Once self-administration had been acquired, the e ffects of a pretreatment with two doses of the opiate antagonist naloxone ( 0.4 mg/kg or 4 mg/kg) were tested. Both doses slightly disrupted self-admin istration on the first 2 days. Only subjects receiving the 4-mg/kg dose exh ibited an extinction of self-administration, related to an increasing numbe r of jump attempts; none of the other opiate withdrawal-associated signs we re observed. Self-administration was reinstated when naloxone was replaced with saline. Conclusions: (1) Medio-ventral NAc is involved in acute reward ing effects of opiates in mice. (2) Neither anterior nor posterior dorsal s triatum seem to participate in these effects. (3) NAc is involved in jumpin g caused by naloxone-induced extinction, a behavior presumably revealing an aversive state associated with the unexpected suppression of reward.