Neuroscience
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Habitual drug-seeking behavior is essential in the transition from recreational drug use to compulsive drug use and is regulated by the dopamine (DA) system of the dorsal striatum (DS). However, a comparative study of the two subtypes of DA receptors, D1 receptors (D1R) and D2 receptors (D2R), which have opposite regulatory functions, in habitual drug-seeking behavior is absent. Moreover, the effects of L-type calcium channels (LTCCs) and the subtypes Cav1.2 and Cav1.3, which are downstream of D1R and D2R, respectively, on habitual drug-seeking behavior have yet to be revealed. ⋯ In addition, the total and membrane Cav1.2 and D1R in the DLS demonstrated higher expression, but the total and membrane Cav1.3 and D2R in the DMS demonstrated lower expression in well-established cocaine habitual behavior animals compared with non-established habitual behavior animals. These results suggested that upregulation of D1R-Cav1.2 signaling may enhance the function of the DLS and that inactivation of D2R-Cav1.3 caused depressed activity in the DMS during expression of habitual cocaine-seeking behavior. The imbalanced function between the DMS and DLS, which causes a shift from the DMS to the DLS, may mediate habitual behaviors.
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Under certain conditions pavlovian memories undergo reconsolidation, whereby the reactivated memory can be disrupted by manipulations such as knockdown of zif268. For instrumental memories, reconsolidation disruption is less well established. Our previous, preliminary data identified that there was an increase in Zif268 in the posterior dorsolateral striatum (pDLS) after expression of an instrumental habit-like 'response' memory, but not an instrumental goal-directed 'place' memory on a T-maze task. ⋯ Zif268 expression increased in the basolateral amygdala after memory reactivation whether a response or place strategy was used during reactivation. We propose that Zif268 expression in the basolateral amygdala may be linked to prediction error, generated by the absence of reward at reactivation. Taken together, these results suggest a complex role for Zif268 in the maintenance of instrumental memories.