Selective inactivation of the ventral hippocampus attenuates cue-induced and cocaine-primed reinstatement of drug-seeking in rats

Abstract

Recent evidence suggests that the hippocampus may have a functional role in mediating relapse to cocaine-seeking behavior. Based on the importance of the ventral CA subfields in mediating reward, the present experiment determined the effects of temporary inactivation of the ventral hippocampus on reinstatement of cocaine-seeking in a rodent model of relapse. Male, Sprague-Dawley rats self-administered i.v. cocaine (0.6 mg/kg/infusion) in the presence of discrete conditioned cues (tone+light) in daily 2-h sessions for ten days. Following seven days of extinction sessions in which neither cues nor drug were available, rats underwent four reinstatement tests in a counterbalanced, within-subjects design. Bilateral microinjections of GABA receptor agonists (baclofen/muscimol (B/M; 1.0 mM/0.1 mM) [corrected] into the ventral hippocampus significantly attenuated cue-induced and cocaine-primed reinstatement compared with vehicle microinjections in the same rats. In contrast, injections just outside the ventral hippocampus did not block either form of reinstatement. Furthermore, inactivation failed to affect responding for food reinforcement, baseline extinction responding, or locomotor activity. These data indicate that the ventral hippocampus plays an important role in the relapse to cocaine-seeking behavior and may interact with key limbic structures previously implicated in cocaine addiction.

Fig. 1

Microinfusion cannula placement within the ventral hippocampus (a) and anatomical controls (b) as verified on cresyl violet-stained sections with representative microphotographs. The symbols represent the most ventral point of the infusion cannula tract for each rat on coronal sections based on the atlas of Paxinos and Watson (1997). Numbers indicate the distance from bregma (mm).

Fig. 2

Responses on the active and inactive levers (mean ± SEM) during extinction (EXT) and conditioned cue-induced or cocaine-primed reinstatement following bilateral infusions of vehicle (VEH) or baclofen-muscimol (B/M) just prior to each test session. (a) Animals with bilateral ventral hippocampus cannulae showed significant increases in responding over EXT levels after VEH, but not B/M infusions (*p < .05, VEH significantly different from EXT; ^†p < .05, B/M significantly different from VEH). (b) Animals with bilateral cannulae outside of the ventral hippocampus showed significant increases in responding over EXT levels after either VEH or B/M infusions (*p < .05, significantly different from EXT).