Biology subjects

Toussaint, A. B.

Publications and source records attributed to Toussaint, A. B..

3 recordsLinked to original sources

bioRxiv2025

Methamphetamine Conditioned Place Preference in Adolescent Mice: Interaction Between Sex and Strain

BackgroundMethamphetamine (METH) use is higher in adolescent women than men. While rodent studies support a sex difference in the reinforcing effects of METH, few have investigated sex differences in the underlying neural circuits, none of which tested rodents during adolescence. AimsInvestigate whether there are sex differences in the rewarding effects of METH in two strains of adolescent mice that are commonly used to generate transgenic lines. Identify changes in associated neural circuits. MethodsWe tested METH-induced conditioned place preference (CPP) in male and female 129Sv/Ev and C57Bl/6 mice during middle adolescence using 1mg/kg of METH. Behaviorally-induced upregulation of c-Fos protein expression was quantified in the nucleus accumbens (NAc) and area CA1 of the hippocampus following the post-conditioning test. ResultsIn C57Bl/6 mice, METH induced CPP in females, but not males. Conversely, METH-induced CPP in 129Sv/Ev males, but not females. In both strains, groups that exhibited CPP had more c-Fos+ cells in the NAc and CA1 when compared to saline-treated control groups. The number of c-Fos+ cells in these two brain regions correlated in groups exhibiting CPP, indicating increased NAc-CA1 communication during retrieval of the conditioned memory. Finally, we found evidence of behavioral sensitization in 129Sv/Ev males only. ConclusionsOur study reveals that the rewarding effects of the METH in adolescent mice are both sex- and strain-dependent, indicating that METH response may result from an interaction between sex-specific and genetic mechanisms. Our findings will be informative when selecting an appropriate background strain in future studies using genetically modified mice.

neuroscience↗

bioRxiv2023

Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring

BackgroundA growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation. MethodsAdult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naive dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naive F1 offspring. ResultsMale, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens. ConclusionsPaternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.

neuroscience↗

bioRxiv2021

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal exposure to morphine on offspring sensitivity to morphine-derived antinociception during painful experiences. To address this question, we constructed a rat pain scale at millisecond timescales to measure mechanical nociception in a multigenerational morphine exposure paradigm. Surprisingly, while developing the pain scale, we found that von Frey hair filaments (VFHs), the most common stimuli used in pain research, are not painful to rats and morphine did not change the touch-like responses elicited by VFHs. We next deployed this novel pain scale to determine whether chronic morphine exposure in sires impacted pain sensitivity in the next generation. Offspring produced from a cross of morphine-treated sires and drug-naive dams, did not show any baseline changes in sensitivity to mechanical nociception. However, morphine-sired male progeny displayed a higher sensitivity to the antinociceptive properties of morphine, as measured by our pain scale. These findings demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent generation.

neuroscience↗