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


OBJECTIVE
To determine whether a reward-sensitive strain of mice (BALB/c) would self-administer morphine directly into the NAc or sub-regions of the dorsal striatum.


METHODS
BALB/c mice were unilaterally implanted with a guide-cannula above either the NAc, the anterior caudate putamen, or the posterior caudate putamen. On each experimental day, a stainless-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) using a spatial discrimination task in a Y maze.


RESULTS
Only the ventro-medial NAc group discriminated between the arm enabling a microinjection of morphine and the neutral arm. Once self-administration had been acquired, the effects 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-administration on the first 2 days. Only subjects receiving the 4-mg/kg dose exhibited an extinction of self-administration, related to an increasing number of jump attempts; none of the other opiate withdrawal-associated signs were observed. Self-administration was reinstated when naloxone was replaced with saline.


CONCLUSIONS
(1) Medio-ventral NAc is involved in acute rewarding effects of opiates in mice. (2) Neither anterior nor posterior dorsal striatum seem to participate in these effects. (3) NAc is involved in jumping caused by naloxone-induced extinction, a behavior presumably revealing an aversive state associated with the unexpected suppression of reward.
David
V
V
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Cazala
P
P
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012201:Reward; D012646:Self Administration / Q000523:psychology
D009294:Narcotics; D009020:Morphine