Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats

Abstract

TTX inactivation of the BLA, ACing, or PL impaired the ability of LT presentations to reinstate extinguished lever pressing for cocaine-paired stimuli. In contrast, inactivation of the IL or the S1BF had no effect on conditioned-cued reinstatement. Furthermore, there was no effect of TTX in any of the tested brain regions on general locomotor activity. CONCLUSIONS. These results support a role for the dorsomedial PFC and the BLA in the circuitry that mediates drug-seeking behavior elicited by cocaine-associated stimuli. Placed within the context of recent studies using drug-primed and stress-induced reinstatement models, we suggest that the dorsomedial PFC may serve as a common link in the neural circuitry underlying reinstatement of drug-seeking behavior.

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

“…Thus, subjects can be used as their own controls. Using an infusion protocol and coordinates identical to those utilized in the present experiments, we have been able to establish functional dissociation between the dmPFC and vmPFC (McLaughlin and See, 2003), as well as between the BLA and the SSbf (McLaughlin and See, 2003) and central nucleus of the amygdala , suggesting that TTX administration resulted in selective inactivation of the target structures in the present study.…”

“…Studies from our laboratory (McLaughlin and See, 2003) have demonstrated that TTX microinfusions into the BLA do not significantly alter general activity during a 1-h locomotor activity test, suggesting that general motor deficits do not account for the effects of BLA inactivation on reinstatement. To further assess possible motor impairing effects of intracranial TTX infusions, we examined the effects of TTX infused into the dmPFC, DH, vmPFC, SStr, or SSbf on general activity.…”

“…Previous research from our laboratory has demonstrated that inactivation of the dmPFC or BLA impairs explicit CSinduced reinstatement of extinguished cocaine-seeking behavior (McLaughlin and See, 2003). Furthermore, inactivation of the dmPFC, but not of the BLA, abolishes cocaine-primed reinstatement of extinguished cocaineseeking behavior (McFarland and Kalivas, 2001).…”

“…Previous research indicates that the dorsomedial prefrontal cortex (dmPFC), basolateral amygdala (BLA), and hippocampus exhibit neuronal activation concomitant with cocaine-seeking behavior in a cocaine-paired environment (Neisewander et al, 2000), and lesions of these structures impair place conditioning, a task dependent on context-reward learning (Tzschentke and Schmidt, 1999;Ferbinteanu and McDonald, 2001;Fuchs et al, 2002b;Meyers et al, 2003). BLA or dmPFC inactivation also impairs explicit CS-induced reinstatement of cocaine seeking (McLaughlin and See, 2003), a behavior based on explicit CS-reward associations ). Furthermore, dmPFC inactivation impairs, whereas BLA inactivation fails to alter, cocaine-primed reinstatement of cocaine-seeking behavior (McFarland and Kalivas, 2001).…”

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

“…Prefrontal cortical and limbic regions are also activated by nicotine-and cocaineassociated cues in rats, as measured by increased gene expression and dopamine release (Schroeder et al, 2001;Ito et al, 2000;Ciccocioppo et al, 2001;Phillips et al, 2003). Lesions of the basolateral amygdala or the prefrontal cortex disrupted responding maintained by cocaine-associated cues (McLaughlin and See, 2003). Intrabasolateral amygdala injections of SCH23390 blocked cue-induced reinstatement of cocaine seeking (See et al, 2001).…”