Social interaction reward in rats has anti‐stress effects

Abstract

Social interaction in an alternative context can be beneficial against drugs of abuse. Stress is known to be a risk factor that can exacerbate the effects of addictive drugs. In this study, we investigated whether the positive effects of social interaction are mediated through a decrease in stress levels. For that purpose, rats were trained to express cocaine or social interaction conditioned place preference (CPP). Behavioural, hormonal, and molecular stress markers were evaluated. We found that social CPP decreased the percentage of incorrect transitions of grooming and corticosterone to the level of naïve untreated rats. In addition, corticotropin-releasing factor (CRF) was increased in the bed nucleus of stria terminalis after cocaine CPP. In order to study the modulation of social CPP by the CRF system, rats received intracerebroventricular CRF or alpha-helical CRF, a nonselective antagonist of CRF receptors. The subsequent effects on CPP to cocaine or social interaction were observed. CRF injections increased cocaine CPP, whereas alpha-helical CRF injections decreased cocaine CPP. However, alpha-helical CRF injections potentiated social CPP. When social interaction was made available in an alternative context, CRFinduced increase of cocaine preference was reversed completely to the level of rats receiving cocaine paired with alpha-helical CRF. This reversal of cocaine preference was also paralleled by a reversal in CRF-induced increase of p38 MAPK expression in the nucleus accumbens shell. These findings suggest that social interaction could contribute as a valuable component in treatment of substance use disorders by reducing stress levels.

Is p38 MAPK Associated to Drugs of Abuse-Induced Abnormal Behaviors?

“…inhibition of p38 failed to block the expression of CPP to morphine. On the other hand, studies that performed intracerebroventricular (icv) injections of SB203580 before cocaine training found no effect on cocaine CPP [ 21 , 22 ]. Consistently, the deletion of p38α in the serotonergic neurons of the dorsal raphe nucleus (DRN) [ 23 ] or the conditional knock-out of p38α MAPK in the dopaminergic neurons of the ventral tegmental area (VTA) [ 24 ] does not affect cocaine CPP, suggesting that the deletion of p38α does not alter the associative learning required for place preference or the rewarding properties of cocaine.…”

“…Finally, social interaction reward has anti-stress effects as social interaction-expressing CPP rats show levels of pp38 similarly to naïve untreated rats [ 34 ]. Indeed, rats receiving corticotropin-releasing factor (CRF) icv injections before cocaine conditioning showed an increase in cocaine CPP, whereas those receiving icv injections of the non-selective antagonist alpha-helical CRF (α CRF) showed a decrease in cocaine CPP [ 22 ]. Remarkably, when social interaction was made available in the alternative compartment, CRF-induced increase of cocaine preference was reversed completely to the level of rats receiving cocaine paired with α CRF.…”

“…Remarkably, when social interaction was made available in the alternative compartment, CRF-induced increase of cocaine preference was reversed completely to the level of rats receiving cocaine paired with α CRF. This reversal of cocaine preference was also paralleled by a reversal in altered behavioral sequencing of grooming, considered as a marker of stress [ 35 ] and by a CRF-induced increase of p38 MAPK expression in the NAc shell [ 22 ] ( Figure 4 ). These results show that the modulation of the CRF system has a direct impact on p38 MAPK expression in the NAc shell, as p38 MAPK expression was increased after icv CRF injections prior to each cocaine conditioning and was decreased after icv injections of α CRF prior to each cocaine conditioning [ 22 ]- Figure 4 .…”

“… Effects of intracerebroventricular (icv) injections of vehicle, corticotropin-releasing factor (CRF), and alpha-helical CRF (α CRF) on ( a ) cocaine preference; on ( b ) associated percentage of incorrect transitions and on ( c ) associated p38 expression in the NAc shell [ 22 ]. Preference score is the time that the rat spent in the stimulus-associated compartment during the test-pretest.…”

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

“…Interestingly, physical contact—but not visual or olfactory cues—is the major rewarding sensory component of the composite stimulus “social interaction” [ 12 , 13 ]. When available as an alternative to drugs of abuse, social interaction rewards prevented reinstatement to cocaine [ 14 , 15 , 16 ], abolished cocaine preference [ 14 , 17 ], and eliminated drug self-administration, even in rats which met the criteria for addiction [ 18 ]. Furthermore, brain regions activated by the cocaine reward and the social interaction reward were shown to mostly overlap [ 19 ].…”