Exogenous administration of Delta-9-Tetrahydrocannabinol affects adult hippocampal neurotransmission in female Wistar rats

Abstract

Delta-9-tetrahydrocannabinol (THC) is the most potent psychoactive element of Cannabis sativa, whose extract has been used for medical, recreational and religious purposes. THC's affects the human cannabinoid system through the activation of its receptors, CB1 and CB2, which are the most abundant in the brain. The CB1 receptor was found in several areas involved in mood, cognitive functions and motor control, including hippocampal formation (HF). THC's side effects are mainly due to its action on brain CB1 receptors. We investigated the effects of THC in female Wistar rats by examining the HF to assess changes in the GABAergic and cholinergic systems. Female Wister rats were subjected to gonadectomy under anesthesia at 8 weeks old. After that, they received estradiol benzoate (EB) and/or THC. Immunohistochemistry was performed to assess the expression of CB1, estradiol receptor alpha (EBα), cholinergic receptor alpha 7 subunit (CHRN), vesicular acetylcholine transporter (VAChT), vesicular glutamate transporter (VGLUT), gamma-aminobutyric acid type A receptor (GABRA) and glutamic acid decarboxylase (GAD). The expression of CB1, VAChT and GAD was reduced ubiquitously by EB, while THC reduces their expression in Oil, but increases in EB groups ubiquitously for CB1 and VAChT groups, but only in CA1 for GAD groups. The opposite is observed regarding the expression of ERα, VGLUT and CHRN. The expression of GABRA is ubiquitously reduced by EB, while THC increases its expression both in Oil and EB groups ubiquitously. Our results may help with decision-making regarding the prescription of low doses of THC as a therapeutical approach.