Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring.

BACKGROUND: Prenatal alcohol exposure is a leading cause of neurobehavioral and neurocognitive deficits collectively known as fetal alcohol spectrum disorders, including eating disorders and increased risk for substance abuse as very common issues. In this context, the present study aimed to assess the interaction between prenatal and lactation alcohol exposure (PLAE) and a high-fat diet (HFD) during childhood and adolescence. METHODS: Pregnant C57BL/6 mice underwent a procedure for alcohol binge drinking during gestation and lactation periods. Subsequently, PLAE female offspring were fed with an HFD for 8 weeks, and thereafter, nutrition-related parameters as well as their response to cocaine were assessed. RESULTS: In our model, feeding young females with an HFD increased their triglyceride blood levels but did not induce overweight compared with those fed with a standard diet. Moreover, PLAE affected how females responded to the fatty diet as they consumed less food than water-exposed offspring, consistent with a lower gain of body weight. HFD increased the psychostimulant effects of cocaine. Surprisingly, PLAE reduced the locomotor responses to cocaine without modifying cocaine-induced reward. Moreover, PLAE prevented the striatal overexpression of cannabinoid 1 receptors induced by an HFD and induced an alteration of myelin damage biomarker in the prefrontal cortex, an effect that was mitigated by an HFD-based feeding. CONCLUSION: Therefore, in female offspring, some effects triggered by one of these factors, PLAE or an HFD, were blunted by the other, suggesting a close interaction between the involved mechanisms.

Cross-reinstatement between 3,4-methylenedioxypyrovalerone (MDPV) and cocaine using conditioned place preference.

3,4-Methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) considered to be a cocaine-like psychostimulant. The substitution of an established illicit drug as cocaine with an NPS is a pattern of use reported among drug users. The aim of this study was to investigate the relationship between cocaine and MDPV in the reinstatement of the conditioned place preference (CPP) paradigm, in order to establish whether there is cross-reinstatement between the two psychostimulants. Four experimental groups of male OF1 mice were subjected to the CPP paradigm: MDPV-MDPV, Cocaine-Cocaine, Cocaine-MDPV, and MDPV-Cocaine. The first drug refers to the substance with which the animals were conditioned (cocaine 10 mg/kg or MDPV 2 mg/kg) and the s to the substance with which preference was reinstated. In parallel, G9a, ΔFosB, CB1 receptor, CDK5, Arc and c-Fos were determined in ventral striatum. MDPV induced CPP at doses from 1 to 4 mg/kg. Although 2 mg/kg MDPV induced a stronger psychostimulant effect than 10 mg/kg cocaine, both doses seemed to be equivalent in their rewarding properties. However, memories associated with MDPV required more time to be extinguished. MDPV and cocaine restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. The fact that MDPV-treated mice show increased ΔFosB protein levels correlates with its longer extinction time and points to the activation of neuroplasticity mechanisms that persist for at least 12 days. Moreover, in these animals, a priming-dose of cocaine can trigger significant neuroplasticity, implying a high vulnerability to cocaine abuse.