Dorsal as well as ventral striatal lesions affect levels of intravenous cocaine and morphine self-administration in rats

Abstract

While the ventral striatum has long been implicated in the rewarding properties of psychomotor stimulants and opiates, little attention has been paid to the possible contribution of more dorsal regions of the striatum. We have thus examined the effects of lesions in three different striatal subregions on cocaine and morphine self-administration. Different groups of rats were trained to self-administer intravenous cocaine (1.0mg/kg/infusion) or morphine (0.5mg/kg/infusion) first under fixed ratio (FR) and then under progressive ratio (PR) schedules of reinforcement. Upon completion of the training, independent groups received bilateral electrolytic or sham lesions of the dorsal portion of the caudate-putamen (dCPu), the ventral portion of the caudate-putamen (vCPu) or the more ventral nucleus accumbens (NAS). Following recovery, they were tested for self-administration of cocaine (0.25, 0.5, 1.0 and 1.5mg/kg/infusion) or morphine (0.125, 0.25, 0.5 and 0.75mg/kg/infusion) under the PR schedule. The PR responding for each drug was significantly reduced in a dose-dependent manner following lesions of dCPu, vCPu and NAS. While the relative effectiveness of these lesions is likely to be specific to the conditions of this experiment, NAS lesions reduced self-administration of each drug to a greater extent than did dCPu or vCPu lesions.

Figure 1

Illustration of the extent of the striatal lesions in rats that self-administered cocaine (A) and morphine (B). The smallest (black fill) and largest (gray fill) lesions of dCPu, vCPu, and NAS are depicted. The line-drawings are modified from Paxinos and Watson [15]. The numbers to the right indicate distance from bregma. The size of the lesions in each hemisphere was determined by examining the coronal section with the most extensive damage per plate.

Figure 2

Bilateral lesions of the dCPu, vCPu, or NAS reduced subsequent cocaine (A) and morphine (B) self-administration under a progressive ratio schedule of reinforcement. Data are shown as group mean (+SEM) total number of lever presses for each of the four different doses of cocaine and morphine tested. Responding was reduced for both drugs in a dose-dependent manner. *, p<0.05–0.001, significantly different from sham lesion controls as determined by post hoc Tukey HSD comparisons following significant ANOVA. n=6–11/group.