Neves Ana M, Leal Sandra, Fonseca Bruno M, Sá Susana I
Department of Biomedicine, Unit of Anatomy, Faculty of Medicine of the University of Porto (FMUP), Alameda Professor Hernani Monteiro, 4200-319 Porto, Portugal.
Associate Laboratory i4HB-Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal.
Int J Mol Sci. 2025 Jun 26;26(13):6144. doi: 10.3390/ijms26136144.
Delta-9-tetrahydrocannabinol (THC) is a psychoactive element of and affects the human cannabinoid system through its receptors, CB1R and CB2R. CB1R was found in several brain areas, including the hippocampal formation (HF), and it is responsible for most THC side effects. We investigated THC's effects in the HF of female Wistar rats to assess changes in its neurotransmission. Female Wister rats ( = 20) were gonadectomized under anesthesia at 8 weeks old. Afterwards, they received estradiol benzoate (EB) and/or THC. Immunohistochemistry was performed to assess the expression of the cholinergic receptor alpha 7 subunit (CHRNA7), the vesicular acetylcholine transporter (VAChT), the vesicular glutamate transporter (VGLUT), the gamma-aminobutyric acid type A receptor (GABRA), the CB1 receptor, and estradiol receptor alpha (EBα). In the HF, the expression of CHRNA7 was increased by EB and by THC in the Oil groups but decreased by THC in the EB groups. The same is true for VGLUT expression in the DG and hilum and for GABRA expression in the hilum. The expression of VAChT and CB1 is reduced by EB, while the concomitant administration of THC increases it. GAD expression is reduced by EB administration in CA1, CA3, and DG. Our results may help with decision-making regarding the prescription of low doses of THC as a therapeutical approach.
Δ-9-四氢大麻酚(THC)是大麻的一种精神活性成分,通过其受体CB1R和CB2R影响人体大麻素系统。CB1R在包括海马结构(HF)在内的多个脑区被发现,它是大多数THC副作用的原因。我们研究了THC对雌性Wistar大鼠海马结构的影响,以评估其神经传递的变化。8周龄雌性Wistar大鼠(n = 20)在麻醉下进行性腺切除。之后,它们接受苯甲酸雌二醇(EB)和/或THC。进行免疫组织化学以评估胆碱能受体α7亚基(CHRNA7)、囊泡乙酰胆碱转运体(VAChT)、囊泡谷氨酸转运体(VGLUT)、γ-氨基丁酸A型受体(GABRA)、CB1受体和雌二醇受体α(EBα)的表达。在海马结构中,EB和油组中的THC增加了CHRNA7的表达,但EB组中的THC降低了CHRNA7的表达。齿状回和海马门中VGLUT的表达以及海马门中GABRA的表达情况也是如此。EB降低了VAChT和CB1的表达,而同时给予THC则增加了它们的表达。在CA1、CA3和齿状回中,EB给药降低了谷氨酸脱羧酶(GAD)的表达。我们的结果可能有助于就低剂量THC作为一种治疗方法的处方做出决策。