Dopamine D sub(3) Receptors in the Basolateral Amygdala and the Lateral Habenula Modulate Cue-Induced Reinstatement of Nicotine Seeking

Dopamine D sub(3) receptors are implicated in cue-induced relapse to drug seeking. We have previously shown that systemic administration of a selective D sub(3) antagonist reduces cue-induced reinstatement of nicotine seeking in rats. The current study sought to investigate potential neural substrates mediating this effect. The D sub(3) antagonist SB-277011-A (0.01-1 mu g/0.5 mu l/side) infused into the basolateral amygdala or the lateral habenula, but not the nucleus accumbens, significantly attenuated cue-induced reinstatement of nicotine seeking. Moreover, infusion of SB-277011-A (1 mu g/0.5 mu l/side) into the basolateral amygdala or lateral habenula had no effect on food self-administration. Together with the finding that systemic SB-277011-A had no effect on extinction responding, this suggests that the effects observed here were on reinstatement and cue seeking, and not due to nonspecific motor activation or contextual-modified residual responding. The further finding of binding of [ super(125)I]7-OH-PIPAT to D sub(3) receptors in the lateral habenula and in the basolateral amygdala is consistent with an important role of D sub(3) receptors in these areas in nicotine seeking. It was also found that systemic administration of the selective D sub(2) antagonist L741626 decreased cue-induced reinstatement, consistent with a role of D sub(2) and D sub(3) receptors in modulating this behavior. The current study supports an important role for D sub(3) receptors in the basolateral amygdala and lateral habenula in cue-induced reinstatement.