Sub-region specific contribution of the ventral hippocampus to drug context-induced reinstatement of cocaine-seeking behavior in rats.

The ventral hippocampus (VH) plays critical roles in cue-induced and cocaine-primed reinstatement of cocaine seeking [Rogers JL, See RE (2007) Neurobiol Learn Mem 87:688-692]. Subregions of the VH make distinct projections to elements of the brain relapse circuitry that mediate drug context-induced reinstatement. Thus, the VH may also critically contribute to this form of cocaine seeking in a subregion-specific manner. Accordingly, this study evaluated the hypothesis that functional inactivation of the ventral hippocampus proper (VHp)-but not of the dentate gyrus (DG)-impairs cocaine seeking elicited by re-exposure to a drug-paired environmental context. Rats were trained to lever press for un-signaled i.v. cocaine infusions (0.15 mg/infusion) in a distinct environmental context (cocaine-paired context) followed by extinction training in a distinctly different context (extinction context). Subsequently, cocaine-seeking behavior (i.e., non-reinforced active lever responding) was assessed in either the previously cocaine-paired context or the extinction context. Rats received bilateral microinfusions of the GABA agonist cocktail, baclofen+muscimol (BM: 1.0/.01 mM), or vehicle into the VHp, DG, or the posterior dorsal hippocampus (pDH; extra-VH control) immediately before each test session. Exposure to the previously cocaine-paired context, but not the extinction context, reinstated extinguished cocaine-seeking behavior following vehicle pretreatment. BM pretreatment administered into the VHp, but not the DG or pDH, significantly attenuated drug context-induced cocaine seeking. These results indicate that the VH contributes to drug context-induced cocaine seeking in a subregion-specific manner, with the functional integrity of the VHp being necessary for memory or motivational aspects of drug-paired environmental stimuli that sustain stimulus control over goal-directed behavior.