Long-term memory of cocaine-associated context: disruption and reinstatement

Abstract

Long-term memory of cocaine-associated context was established by conditioned place preference learning. After 1 week, exposure to context in the absence of cocaine (memory retrieval) was paired with one of the following treatments: saline, scopolamine (muscarinic acetylcholine receptor antagonist), dizocilpine (MK-801; noncompetitive N-methyl-D-aspartate antagonist) or D-cycloserine (partial N-methyl-D-aspartate agonist). In subsequent conditioned place preference tests, place preference was suppressed in the drug-treated groups but not saline-treated groups. Results suggest that the amnesic agents, scopolamine and MK-801, disrupted reconsolidation of cocaine-associated contextual memory. In contrast, the mnemonic agent D-cycloserine might have facilitated extinction learning during context exposure in the absence of cocaine. Challenge administration of cocaine reinstated place preference in all groups except the MK-801 group, suggesting that suppression of conditioned response may or may not suppress memory evoked by drug-context reexposure.

d-cycloserine in the basolateral amygdala prevents extinction and enhances reconsolidation of odor-reward associative learning in rats

“…It has also been shown that pre-extinction DCS administration facilitated fear extinction, although extinguished fear was normally renewed, suggesting that the drug may modestly facilitate extinction learning, but does not destroy the potential for relapse (Woods & Bouton, 2006). Moreover, the current results contrast with previous research assessing the impact of DCS administered after extinction learning, which indicated enhanced extinction consolidation of different drug-seeking behaviors after intra-BLA or systemic DCS injections (Botreau et al, 2006;Kelley et al, 2007;Nic Dhonnchadha et al, 2009;Paolone et al, 2009;Thanos et al, 2009). Nevertheless, additional reports have also shown other inconsistencies in the capacity of DCS to enhance extinction consolidation.…”

“…Recent research has reported the role of DCS in the extinction of learned behavior involving appetitive stimuli, such as drug-seeking behavior, suggesting that systemic administration of DCS facilitates the extinction consolidation of self-administration and conditioned place preference (CPP) associated to different drugs (Botreau, Paolone & Stewart, 2006;Kelley, Anderson & Itzhak, 2007;Nic Dhonnchadha et al, 2010;Paolone, Botreau & Stewart, 2009;Thanos, Bermeo, Wang & Volkow, 2009;Thanos, Bermeo, Wang & Volkow, 2011) and enhances the persistence of extinction (Groblewski, Lattal & Cunningham, 2009). In contrast to such reports, a recent study showed that pretreatment with systemic DCS prior to extinction training had no effect on the extinction and subsequent reinstatement of morphineinduced CPP (Lu, Wu, Zhang, Ai & Li, 2011).…”

Inhibition of β-Adrenergic Receptors Induces a Persistent Deficit in Retrieval of a Cocaine-Associated Memory Providing Protection against Reinstatement

“…In our hands, propranolol treatment resulted in a permanent retrieval deficit, as the CPP did not re-emerge after 14 days in a test for spontaneous recovery or after a priming injection of cocaine. This latter effect is remarkable, as cocaine has been shown to reliably induce reinstatement of a CPP after extinction (Kelley et al, 2007;Mantsch et al, 2010;Mueller and Stewart, 2000;RodriguezArias et al, 2009). Because the passage of time and cocaine itself did not reinstate the CPP, we conclude that retrieval of the original association between cocaine and the conditioning context was disrupted.…”

“…A priming injection of cocaine has been shown to reliably induce reinstatement of a CPP after extinction (Kelley et al, 2007;Mantsch et al, 2010;Mueller and Stewart, 2000;Rodriguez-Arias et al, 2009). Behaviorally, both propranolol treatment and extinction training abolish the expression of a CPP; hence, in experiment 5, we determined whether the retrieval deficit induced by propranolol would prevent reinstatement of a CPP to a priming injection of cocaine.…”

Neuroanatomical Structures Underlying the Extinction of Drug-Seeking Behavior

“…This provides a tool for measuring the motivational salience of the cue, independent of the psychomotor effects of the drug. In a slightly different paradigm, context-induced or contextual reinstatement examines the associative strength of the physical environment in mediating drug-seeking behavior [52,58,[60][61][62][63][64]. Here, animals undergo extinction training in an experimental apparatus that is contextually unique from the apparatus where self-administration was acquired.…”