Post-retrieval propranolol treatment does not modulate reconsolidation or extinction of ethanol-induced conditioned place preference

Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 Sam Jackson Park Road, Portland, OR 97239, USA.
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 04/2012; 101(2):222-30. DOI: 10.1016/j.pbb.2012.01.009
Source: PubMed


The reconsolidation hypothesis posits that established emotional memories, when reactivated, become labile and susceptible to disruption. Post-retrieval injection of propranolol (PRO), a nonspecific β-adrenergic receptor antagonist, impairs subsequent retention performance of a cocaine- and a morphine-induced conditioned place preference (CPP), implicating the noradrenergic system in the reconsolidation processes of drug-seeking behavior. An important question is whether post-retrieval PRO disrupts memory for the drug-cue associations, or instead interferes with extinction. In the present study, we evaluated the role of the β-adrenergic system on the reconsolidation and extinction of ethanol-induced CPP. Male DBA/2J mice were trained using a weak or a strong conditioning procedure, achieved by varying the ethanol conditioning dose (1 or 2 g/kg) and the number of ethanol trials (2 or 4). After acquisition of ethanol CPP, animals were given a single post-retrieval injection of PRO (0, 10 or 30 mg/kg) and tested for memory reconsolidation 24 h later. Also, after the first reconsolidation test, mice received 18 additional 15-min choice extinction tests in which PRO was injected immediately after every test. Contrary to the prediction of the reconsolidation hypothesis, a single PRO injection after the retrieval test did not modify subsequent memory retention. In addition, repeated post-retrieval administration of PRO did not interfere with extinction of CPP in mice. Overall, our data suggest that the β-adrenergic receptor does not modulate the associative processes underlying ethanol CPP.

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    • "Memories relevant to relapse in alcohol addiction do appear to undergo reconsolidation (Barak et al, 2013; von der Goltz et al, 2009; Wouda et al, 2010), but there have been inconsistent reports in the literature regarding the dependence of this process on β-adrenergic signaling. Those few studies that have investigated the effects of propranolol on alcohol-associated memories have shown that propranolol does not disrupt the reconsolidation of the memories underlying alcohol-conditioned place preference (Font and Cunningham, 2012), but does disrupt the reconsolidation of pavlovian memories that contribute to cue-induced relapse to alcohol-seeking (Wouda et al, 2010). As cue-induced relapse can be behaviorally deconstructed into the constituent processes of pavlovian conditioned approach, conditioned motivation and conditioned reinforcement (the 'three routes to relapse' -see Milton et al, 2010), this latter report appears to be inconsistent with the finding that propranolol does not disrupt the reconsolidation of the memories underlying pavlovian conditioned approach or conditioned motivation for alcohol-associated cues (Milton et al, 2012). "
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    ABSTRACT: Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self-administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The β-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories.
    Neuropsychopharmacology 08/2015; DOI:10.1038/npp.2015.248 · 7.05 Impact Factor
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    • "The 1 g/kg dose of EtOH was used with 1 and 2 mg/kg nicotine because these were the doses used in our previous work showing greater-than-additive effects on locomotor activity (Gubner et al., 2013). In addition, it was desirable to use a lower dose of EtOH that would be less likely to induce maximal CPP on its own (Font and Cunningham, 2012). On the preference test days, mice were injected with saline (no drug on board) and placed in the CPP apparatus for 30 minutes with both floor types (grid and hole) present. "
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    ABSTRACT: Background One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co-abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH-induced CPP.Methods The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well-established CPP procedure chosen specifically for examining alterations in the development of EtOH-induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH.ResultsNeither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH-induced CPP was not affected by co-administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH-induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data.Conclusions These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward.
    Alcoholism Clinical and Experimental Research 01/2015; 39(1). DOI:10.1111/acer.12590 · 3.21 Impact Factor
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    • "Through a classical Pavlovian conditioning, it is possible to evaluate the capacity of ethanol rewarding effect to induce changes in the conditioned behavior (Tzschentke, 1998, 2007). The CPP paradigm allows the study of environment-evoked relapse based on the animals' approach to the conditioned environment after a period of abstinence (Liu et al., 2008; Aguilar et al., 2009) and it has been used to investigate and manipulate drugs of abuse-related memories (Monfils et al., 2009; Font and Cunningham, 2012; Groblewski and Cunningham, 2012; Xue et al., 2012). "
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    ABSTRACT: Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.
    Frontiers in Behavioral Neuroscience 08/2014; 8:267. DOI:10.3389/fnbeh.2014.00267 · 3.27 Impact Factor
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