Higher sensitivity to the conditioned rewarding effects of cocaine and MDMA in High-Novelty-Seekers mice exposed to a cocaine binge during adolescence

Abstract

Cocaine binge administration during adolescence induces a higher sensitivity to the rewarding effects of MDMA and cocaine in HNS mice in adulthood. This may explain the greater vulnerability often seen among individuals exposed early in life to drugs of abuse.

The novelty-seeking phenotype modulates the long-lasting effects of adolescent MDMA exposure

“…A recent study has shown that the novelty-seeking phenotype does not significantly correlate with either acquisition or drugseeking parameters of MDMA self-administration in rats [40]. However, following cocaine treatment, we have observed that an increase in the conditioned rewarding effects of MDMA is observed only in HNS mice, while no differences are observed in mice exposed to ethanol during adolescence [38,39]. Moreover, the numerous methodological differences make these studies very difficult to compare.…”

“…Head-dipping in the hole-board test has been proposed as a useful measure with which to examine the relationship between novelty-seeking and drug abuse [53]. Previous studies show that the hole-board test is more effective in identifying adolescent mice that will be sensitive to the conditioned rewarding effects of cocaine on the long-lasting effects of ethanol or cocaine [37][38][39]. The median was used in order to classify the mice as HNS versus LNS, as this is a standard measure when a set of data has been arranged in order of magnitude and is less affected by outliers.…”

“…We have previously demonstrated that sensitivity to the conditioned reinforcing effects of cocaine depends on the level of NS of the mice, with stronger responses being observed in high novelty seekers (HNS) [36,37]. Moreover, we have observed that the long-term effects of adolescent exposure to cocaine or ethanol are also modulated by the NS trait in mice; only HNS exposed to cocaine during adolescence presented CPP with non-effective doses of cocaine or MDMA [38]. Comparable results were obtained in mice exposed to a model of chronic intermittent ethanol administration during adolescence, in which CPP was reinstated only in HNS [39].…”

“…We have recently reported that the NS trait also modulates the longlasting effects of exposure to cocaine or ethanol during adolescence. Chronic administration of cocaine during adolescence induced acquisition of CPP with non-effective doses in HNS adult mice only [38]. Similarly, although a chronic intermittent pattern of ethanol consumption during adolescence increased the rewarding effects of cocaine in all the treated mice, more sessions were needed to extinguish the preference in HNS, which were the only mice in which CPP was reinstated with a priming dose of cocaine [39].…”

“…with 1 mg/kg of cocaine hydrochloride (Laboratorios Alcaliber S. A. Madrid, Spain) and 1 mg/kg of MDMA in a volume of 0.01 ml/g. The doses selected to induce CPP were based on previous studies in which they did not induce CPP [11,29,38,[41][42][43]. We employed a non-effective dose in order to determine the sensitizing effect of adolescent MDMA treatment on the conditioned reinforcing effects of cocaine and MDMA.…”