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

Int J Mol Sci. 2021 Feb 7;22(4):1666. doi: 10.3390/ijms22041666.


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.

Keywords: behavior; cannabis; dopamine; electrophysiology; neurodevelopment; neuropsychiatric disorders; sex.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Dopamine / metabolism*
  • Dronabinol / toxicity*
  • Female
  • Hallucinogens / toxicity
  • Limbic System / drug effects*
  • Limbic System / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / pathology


  • Hallucinogens
  • Dronabinol
  • Dopamine