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Abstract
We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Here we show that non-contingent cocaine or methylphenidate injections (UCS retrieval) 1 h before the extinction sessions decreases cocaine-priming-induced reinstatement, spontaneous recovery, and renewal of cocaine seeking in rats. Unlike the CS-based memory retrieval-extinction procedure, the UCS memory retrieval manipulation decreases renewal and reinstatement of cocaine seeking in the presence of cocaine cues that were not present during extinction training and also decreases cocaine seeking when the procedure commences after 28 days of abstinence. The inhibitory effect of the UCS retrieval manipulation on cocaine-priming-induced reinstatement is mediated by regulation of AMPA-receptor endocytosis in the basolateral amygdala. The UCS memory retrieval-extinction procedure has superior relapse prevention characteristics than the CS memory retrieval-extinction procedure and could be a promising method for decreasing relapse in human addicts.
Highlights
We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans
On the basis of these limitations and results demonstrating that the inhibitory effects of neuropharmacological manipulations on both fear conditioning[18] and drug CPP19,20 after memory retrieval was induced by the unconditioned stimulus (UCS), we have recently developed a UCS memory retrieval-extinction procedure and demonstrated its effect on inhibition of Pavlovian conditioned fear in both rats and humans[21]
We compared the effect of the novel UCS memory retrievalextinction procedure to our recently established CS memory retrieval-extinction procedure[13] on reinstatement of cocaine seeking induced by cocaine-priming injections, spontaneous recovery of cocaine seeking after extinction, and renewal of cocaine seeking after extinction of cocaine self-administration in a different context
Summary
We recently reported that a conditioned stimulus (CS) memory retrieval-extinction procedure decreases reinstatement of cocaine and heroin seeking in rats and heroin craving in humans. Investigators have used a CS memory retrievalextinction procedure to prevent recovery of fear after extinction in rats[9,10] and humans[11,12] In these studies, reinstatement, renewal, and spontaneous recovery of fear responding were decreased by brief exposure to cues previously paired with footshock (a retrieval manipulation) if that exposure was followed 10 min or 1 h later by repeated exposure to the same cues in longer-duration extinction sessions. On the basis of these limitations and results demonstrating that the inhibitory effects of neuropharmacological manipulations on both fear conditioning[18] and drug CPP19,20 after memory retrieval was induced by the unconditioned stimulus (UCS), we have recently developed a UCS memory retrieval-extinction procedure and demonstrated its effect on inhibition of Pavlovian conditioned fear in both rats and humans[21]. We modified the UCS memory retrieval-extinction procedure to study its effect on reinstatement, spontaneous recovery, and renewal of cocaine seeking in an operant rat model of drug relapse[22]
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