Involvement of cAMP-Dependent Protein Kinase in the Nucleus Accumbens in Cocaine Versus Social Interaction Reward

Evidence suggests that PKA activity in the nucleus accumbens (NAc) plays an essential role in reward-related learning. In this study, we investigated whether PKA is differentially involved in the expression of learning produced by either natural reinforcers or psychostimulants. For that purpose, we inhibited PKA through a bilateral infusion of Rp-cAMPS, a specific PKA inhibitor, directly into the NAc. The effects of PKA inhibition in the NAc on the expression of concurrent conditioned place preference (CPP) for cocaine (drug) and social interaction (natural reward) in rats were evaluated. We found that PKA inhibition increased the expression of cocaine preference. This effect was not due to altered stress levels or decreased social reward. PKA inhibition did not affect the expression of natural reward as intra-NAc Rp-cAMPS infusion did not affect expression of social preference. When rats were trained to express cocaine or social interaction CPP and tested for eventual persisting preference 7 and 14 days after CPP expression, cocaine preference was persistent, but social preference was abolished after the first test. These results suggest that PKA in the NAc is involved in drug reward learning that might lead to addiction and that only drug, but not natural, reward is persistent.

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Rewarding Social Interaction in Rats Increases CaMKII in the Nucleus Accumbens

Biomedicines ◽

10.3390/biomedicines9121886 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1886

Author(s):

Inês M. Amaral ◽

Laura Scheffauer ◽

Angelika B. Langeder ◽

Alex Hofer ◽

Rana El Rawas

Keyword(s):

Social Interaction ◽

Nucleus Accumbens ◽

Dependent Protein Kinase ◽

The Core ◽

Calcium Calmodulin Dependent ◽

Seeking Behavior ◽

Natural Rewards ◽

Dependent Protein ◽

The One

Calcium/calmodulin-dependent protein kinase II (CaMKII) is known to be involved in the sensitized locomotor responses and drug-seeking behavior to psychostimulants. However, little is known about the contribution of CaMKII signaling in the nucleus accumbens (NAc) in natural rewards such as social interaction. The present experiments explored the implication of CaMKII signaling in drug versus natural reward. In the NAc of rats expressing cocaine or social interaction conditioned place preference (CPP), αCaMKII activation was induced in those expressing social interaction but not cocaine CPP. In order to investigate the role of NAc CaMKII in the expression of reward-related learning of drug versus non-drug stimuli, we inhibited CaMKII through an infusion of KN-93, a CaMKII inhibitor, directly into the NAc shell or core, before the CPP test in a concurrent paradigm in which social interaction was made available in the compartment alternative to the one associated with cocaine during conditioning. Whereas vehicle infusions led to equal preference to both stimuli, inhibition of CaMKII by a KN-93 infusion before the CPP test in the shell but not the core of the NAc shifted the rats’ preference toward the cocaine-associated compartment. Altogether, these results suggest that social interaction reward engages CaMKII in the NAc.

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Effects of voluntary ethanol intake on the expression of Ca2+/calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens

Neuroreport ◽

10.1097/00001756-200112210-00054 ◽

2001 ◽

Vol 12 (18) ◽

pp. 4133-4137 ◽

Cited By ~ 24

Author(s):

Kaushik Misra ◽

Adip Roy ◽

Subhash C. Pandey

Keyword(s):

Nucleus Accumbens ◽

Protein Kinase ◽

Ethanol Intake ◽

Dependent Protein Kinase ◽

Dependent Protein ◽

Rat Nucleus Accumbens

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8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus accumbens amphetamine in rats

Acta Neuropsychiatrica ◽

10.1017/neu.2013.37 ◽

2013 ◽

Vol 26 (2) ◽

pp. 104-111 ◽

Cited By ~ 1

Author(s):

Sung Woo Park ◽

Ali Roohbakhsh ◽

Richard J. Beninger

Keyword(s):

Nucleus Accumbens ◽

Protein Kinase ◽

Dopamine Receptor ◽

Conditioned Place Preference ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Place Preference ◽

Dependent Protein Kinase ◽

Cyclic Monophosphate ◽

Dependent Protein

ObjectivesDopamine receptor-mediated 3′,5′-cyclic adenosine monophosphate (cAMP)-dependent intracellular signalling is important for reward-related learning. cAMP activates cAMP-dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). We tested the hypothesis that reward-related learning may be mediated by Epac.MethodsWe evaluated conditioned place preference (CPP) on the basis of nucleus accumbens (NAc) injections of amphetamine (20 μg/0.5 μl/side) plus Sp-adenosine 3′,5′-cyclic monophosphorothioate triethylamanine (Sp-cAMPS) (0.1, 1.0, 10, 15, 20 μg/0.5 μl/side), an activator of both PKA and Epac, or amphetamine (20 μg) plus 8-(4-chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate (8-pCPT) (0.73, 1.27, 1.45, 2.89, 5.78, 11.56 μg/0.5 μl/side), an activator of Epac.ResultsIn agreement with previous results, Sp-cAMPS dose-dependently impaired CPP. 8-pCPT impaired CPP at one dose (1.45 μg/0.5 μl/side) and we replicated this effect three times.ConclusionThe results implicate Epac in the acquisition of reward-related learning.

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