Conditioned place preference for social interaction in rats: contribution of sensory components

A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus “social interaction” contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm2 prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus “social interaction” is touch (taction)

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

AbstractWe have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens

Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction

Differential Effects of Accumbens Core vs. Shell Lesions in a Rat Concurrent Conditioned Place Preference Paradigm for Cocaine vs. Social Interaction

A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. Among these activities, social interaction is doubly important because treatment adherence itself depends on it. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male conspecific (i) reversed CPP from cocaine to social interaction despite continuing cocaine training and (ii) prevented the reinstatement of cocaine CPP. In the present study, we investigated if the two subregions of the nucleus accumbens (Acb), i.e., the core (AcbC) and the shell (AcbSh), would differentially affect CPP for cocaine vs social interaction.Animals were concurrently trained for CPP pairing cocaine with one compartment and social interaction with the other (i.e., mutually exclusive stimulus presentation during training). Excitotoxic lesioning of the AcbC or the BLA shifted CPP toward social interaction, whereas AcbSh inactivation shifted CPP toward cocaine.Overall, our findings suggest that inactivation of the AcbC or the BLA is sufficient to shift CPP away from a drug of abuse toward social interaction. Lesioning the AcbSh produced the opposite effect

Handbooks of pharmacology and toxicology

The overwhelming majority of problem drinkers (i.e., alcohol-abusing patients) and alcohol-dependent patients are first seen by physicians in general practice, in a primary care setting, or at nonpsychiatric inpatient facilities, such as departments of internal medicine or surgery. If you work in such a setting, this book is for you. It is my firm belief that comprehensive treatment of your alcohol-abusing or alcohol-dependent patient lies within your grasp and should, for that matter, ultimately lie in the hands of one therapist; this book will help you to acquire the necessary expertise to achieve this. You will, in all likelihood, find that you want to delegate some aspects of the medical care of your alcoholic patient to more specialized partners who might have more resources than you with respect to time, logistics, and specialized training. Still, it is you who can give crucial help to your patient who is experiencing alcohol-related problems, right from the first contact and interview. And, let’s face it, you have to do it — you are the one your patient usually first contacts and not necessarily because he or she is aware of her/his alcohol problem. Not yet. With the help of this handbook, you will acquire the necessary skills to help him/her recognize the underlying alcohol problem. Two chapters (Chapter 1, First Contact and Early Intervention; Chapter 9, Psychotherapy) are dedicated to explaining which psychological problems you are most likely to encounter at every stage of the disease and how to best cope with the negative emotions that the alcohol-dependent patient — so severely affected by the disease — will most likely induce in you, his physician

E- Social Interaction and Cocaine Conditioning in Mice Increase Spontaneous Spike Frequency in the Nucleus Accumbens or Septal Nuclei as Revealed by Multielectrode Array Recordings

findings suggest that place preference conditioning for both drug and natural rewards may induce persistent changes in neuronal network activity in the nucleus accumbens and the septum that are still preserved in acute slice preparations

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquistion/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the granular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning leraning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.Funding Agencies|Austrian Science Fund (FWF)|M1169-B18P23824-B18W1206-B18|Verein fur Experimentelle Psychiatrie, psychotherapic, und Pharmakologie (VEPPP)||</p