Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.

Recreational Activities and d-Amphetamine Effects in High and Low Sensation Seekers

This study examined the behavioral effects of d-amphetamine and recreational activities, alone and in combination, in high and low impulsive sensation seekers. Healthy 18-27 year-old participants, scoring in the upper (N=8) or lower (N=8) third of college students on the impulsive sensation-seeking scale of the Zuckerman-Kuhlman Personality Questionnaire, completed eight test days in which sessions were completed before (i.e., baseline) and 60, 120 and 180 minutes after d-amphetamine (0, 10 mg/70 kg) administration. Between sessions, subjects completed recreational activities (movies, music, reading, videogames) identified as high or low in sensation value. Each of four conditions (low and high sensation value activities combined with placebo and active drug) was administered under double-blind conditions on 2 days according to a randomized-block design. Typical stimulant-like cardiovascular and task performance effects were engendered by d-amphetamine; consistent with previous research, the magnitude of drug effects were greater among high sensation seekers. High sensation value activities engendered independent stimulant-like effects on subject ratings. These results suggest that d-amphetamine and high sensation stimulus materials may activate a common neurobiological substrate, likely the mesolimbic dopamine system, and that individual differences in sensation seeking status play a role in vulnerability to stimulant drug abuse.

Prenatal THC does not affect female mesolimbic dopaminergic system in preadolescent rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes towards it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase of dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related-behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.HighlightsPCE female offspring do not manifest a disease-relevant phenotypePrenatal THC does not affect female dopaminergic neuronsPCE female mesolimbic dopamine function is less responsive to acute THC