Overexpression of ASIC1A in the nucleus accumbens of rats potentiates cocaine-seeking behavior.

Acid-sensing ion channels (ASICs) are abundantly expressed in the nucleus accumbens core (NAcore), a region of the mesolimbocortical system that has an established role in regulating drug-seeking behavior. Previous work shows that a single dose of cocaine reduced the AMPA-to-NMDA ratio in Asic1a mice, an effect observed after withdrawal in wild-type mice, whereas ASIC1A overexpression in the NAcore of rats decreases cocaine self-administration. However, whether ASIC1A overexpression in the NAcore alters measures of drug-seeking behavior after the self-administration period is unknown.

Extinction of Cocaine Seeking Requires a Window of Infralimbic Pyramidal Neuron Activity after Unreinforced Lever Presses.

The infralimbic cortex (IL) mediates extinction learning and the active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we used activity-guided optogenetics in male Sprague Dawley rats to silence IL pyramidal neurons optically for 20 s immediately after unreinforced lever presses during early extinction training after cocaine self-administration.

D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner.

Evidence suggests that the infralimbic cortex (IL), a subregion of the ventromedial prefrontal cortex (vmPFC), suppresses cocaine-seeking behavior in a self-administration paradigm, whereas the more anterior vmPFC subregion, the medial orbitofrontal cortex (mOFC), has received very little attention in this regard. Despite the established dopaminergic innervation of the vmPFC, whether dopamine receptor blockade in each subregion alters the reinstatement of cocaine seeking is unclear. To address this issue, male Sprague-Dawley rats underwent 2 weeks of cocaine self-administration, followed by extinction training and reinstatement testing.

The infralimbic and prelimbic cortices contribute to the inhibitory control of cocaine-seeking behavior during a discriminative stimulus task in rats.

The infralimbic and prelimbic (IL and PL, respectively) regions of the medial prefrontal cortex regulate the control of drug-seeking behavior. However, their roles in cocaine seeking in a discriminative stimulus (DS)-based self-administration task are unclear. To address this issue, male Sprague Dawley rats were trained on a DS task in which, on a trial-by-trial basis, a DS+ indicated that a lever press would produce a cocaine infusion, whereas a distinct DS- indicated that a lever press would produce nothing.