Post-retrieval disruption of a cocaine conditioned place preference by systemic and intrabasolateral amygdala β₂- and α₁-adrenergic antagonists

Abstract

Previous work has demonstrated post-retrieval impairment in associative learning paradigms, including those mediated by drugs of abuse, using nonspecific b-adrenergic receptor (b-AR) antagonists. Remarkably little is known about the role of the specific b-AR subtypes, or other adrenergic receptors, in these effects. The current study examined the effects of b 1 and b 2 , as well as a 1 -adrenergic receptor antagonism following retrieval of a cocaine conditioned place preference (CPP). We found that rats administered the b 2 antagonist ICI 118,551 (8 mg/kg intraperitoneal [IP]) or the a 1 antagonist prazosin (1 mg/kg IP) following a drug-free test for CPP showed attenuated preference during a subsequent test, while the b 1 antagonist betaxolol (5 or 10 mg/kg IP) and a lower dose of prazosin (0.3 mg/kg IP) had no effect. Furthermore, posttest microinfusion of ICI 118,551 (6 nmol/side) or prazosin (0.5 nmol/side) into the basolateral amygdala (BLA) also impaired a subsequent preference. Systemic or intra-BLA ICI 118,551 or prazosin administered to rats in their home cages, in the absence of a preference test, had no effect on CPP 24 h later. ICI 118,551 also attenuated the FOS response in the BLA induced by the CPP test. These results are the first to demonstrate a role for a 1 -and b 2 -specific adrenergic mechanisms in post-retrieval memory processes. These systemic and site-specific injections, as well as the FOS immunohistochemical analyses, implicate the importance of specific noradrenergic signaling mechanisms within the BLA in post-retrieval plasticity.

Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o-coupled β2-adrenergic signaling

“…Further, stimulating b 2 receptors in the prefrontal cortex can enhance working memory, while stimulating b 1 receptors impairs working memory (Ramos et al 2005(Ramos et al , 2008. Other mnemonic roles for b 2 signaling that have been recently described include reconsolidation and stress-induced reinstatement of conditioned place preference for cocaine (Bernardi et al 2009;Mantsch et al 2010).…”

Chemogenetic and Optogenetic Activation of Gαs Signaling in the Basolateral Amygdala Induces Acute and Social Anxiety-Like States

“…Although consistent with recent reports suggesting that β-adrenergic receptors do not mediate noradrenergic dependent real-time aversion , it is somewhat surprising that there was no effect in the CPA assay. Given the role of the BLA and β-adrenergic receptors in emotional and stressful memory (Bernardi et al, 2009;McGaugh, 2004;Wu et al, 2014), it is possible that our stimulus was not aversive or salient enough. Future studies could expand on the photostimulation parameters, and other learning assays, such as fear conditioning, may be more suited.…”

Compound Stimulus Presentation and the Norepinephrine Reuptake Inhibitor Atomoxetine Enhance Long-Term Extinction of Cocaine-Seeking Behavior

“…For example, LaLumiere et al (2010) found that repeated post-training administration of the b2-adrenergic agonist clenbuterol within the infralimbic cortex enhanced retention of extinction, as evidenced by lower responding in subsequent sessions. Other past work has found that interference with the NE system can disrupt stable memory formation as post-retrieval administration of propranolol can impair cocaine-conditioned place preference (Bernardi et al, 2006(Bernardi et al, , 2009Fricks-Gleason and Marshall, 2008) or conditioned reinforcement (Milton et al, 2008). These effects have been attributed to disrupted reconsolidation.…”

“…A role for NE in extinction learning has been demonstrated for extinction of conditioned fear (Cain et al, 2004;Morris and Bouton, 2007) and operant responding for food (Janak and Corbit, 2010). Similarly, recent studies found that NE is important for consolidation of extinction in both cocaine-conditioned place preference (Bernardi and Lattal, 2010;Bernardi et al, 2009;Brenhouse et al, 2010) and self-administration procedures (LaLumiere et al, 2010) using post-training administrations of adrenergic drugs. We hypothesized that the benefit to extinction produced by extinction of a compound cue may also rely on NE activity and, therefore, examined if extinction of cocaine seeking could be enhanced or impaired by pre-training manipulations of the NE system.…”