Adolescent rats that binge drink alcohol show reduced levels of the neuropeptide CGRP in brain regions involved in emotion and reward (medial prefrontal cortex, nucleus accumbens, amygdala) and increased CGRP in the brainstem. These rats also display heightened responses to rewarding and painful stimuli, reduced social drive, and lower corticosterone levels. Treatment with cannabidiol (40 mg/kg) before each drinking session reduced alcohol consumption and preference, normalized CGRP expression in corticolimbic areas, and corrected the abnormal reward and aversion responses as well as glucocorticoid levels. CGRP may mediate and be a target of alcohol binge drinking, and cannabidiol shows promise for limiting adolescent binge drinking and its behavioral and neuroendocrine consequences.
Long-chain omega-3 polyunsaturated fatty acids (LC-ω-3-PUFAs) given during pregnancy and lactation prevented memory deficits caused by prenatal THC exposure in adolescent rats. THC exposure during gestation impaired hippocampus-dependent memory and disrupted excitatory/inhibitory balance in a sex-dependent manner. Supplementation with an omega-3-enriched diet restored memory performance in both sexes. In males, the fatty acids counteracted THC-induced synaptic hyperexcitability by normalizing expression of plasticity markers and endocannabinoid enzymes. In females, they rebalanced a THC-induced inhibitory shift by reducing certain synaptic protein and enzyme levels. The findings suggest perinatal omega-3 supplementation is a safe nutritional strategy to protect against THC-induced neurodevelopmental harm by restoring endocannabinoid system balance and supporting sex-specific brain plasticity.
Prenatal exposure to THC, the main psychoactive component of cannabis, disrupts spatial memory and alters the balance of excitatory and inhibitory signaling in the hippocampus in a sex-specific manner. In adolescent male rats, THC exposure impaired memory retrieval and flexibility, reduced the density of a key type of inhibitory interneuron (CCK-positive basket cells), and increased markers of neuroplasticity. In females, memory retrieval was delayed but flexibility was spared, and the density of those inhibitory interneurons increased. The findings suggest male offspring are more vulnerable to prenatal THC's effects on memory processing, with sex-specific changes in synaptic plasticity and excitatory/inhibitory balance.