Acute Delta 9-tetrahydrocannabinol administration differentially alters the hippocampal opioid system in adult female and male rats.
Kyle A Windisch, Sanoara Mazid, Megan A Johnson, Elina Ashirova, Yan Zhou, Lennox Gergoire, Sydney Warwick, Bruce S McEwen, Mary Jeanne Kreek, Teresa A Milner
Synapse (New York, N.Y.) October 2021 DOI: 10.1002/syn.22218 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult female and male Sprague-Dawley rats |
| Dose | 5 mg/kg, i.p. |
| Duration | 1 h |
| Topics | Cannabis |
| Keywords | Delta opioid receptor Hippocampal ca3 Sex differences Δ9-tetrahydrocannabinol |
| Key findings | Acute THC (5 mg/kg, i.p., 1 h) produced sex-specific changes in the hippocampal opioid system: in high-estrogen females it lowered mossy fiber Leu-Enkephalin and raised phosphorylated delta and mu opioid receptors in CA3 regions, while in males it internalized mu receptors in parvalbumin interneuron dendrites. In both sexes THC redistributed delta receptors near the plasma membrane of CA3 pyramidal dendrites, in a sex-dependent pattern. |
Abstract
Our prior studies demonstrated that the rat hippocampal opioid system can undergo sex-specific adaptations to external stimuli that can influence opioid-associated learning processes. This opioid system extensively overlaps with the cannabinoid system. Moreover, acute administration of Δ9 Tetrahydrocannabinoid (THC), the primary psychoactive constituent of cannabis, can alter cognitive behaviors that involve the hippocampus. Here, we use light and electron microscopic immunocytochemical methods to examine the effects of acute THC (5 mg/kg, i.p., 1 h) on mossy fiber Leu-Enkephalin (LEnk) levels and the distribution and phosphorylation levels of delta and mu opioid receptors (DORs and MORs, respectively) in CA3 pyramidal cells and parvalbumin dentate hilar interneurons of adult female and male Sprague-Dawley rats. In females with elevated estrogen states (proestrus/estrus stage), acute THC altered the opioid system so that it resembled that seen in vehicle-injected females with low estrogen states (diestrus) and males: (1) mossy fiber LEnk levels in CA2/3a decreased; (2) phosphorylated-DOR levels in CA2/3a pyramidal cells increased; and (3) phosphorylated-MOR levels increased in most CA3b laminae. In males, acute THC resulted in the internalization of MORs in parvalbumin-containing interneuron dendrites which would decrease disinhibition of granule cells. In both sexes, acute THC redistributed DORs to the near plasma membrane of CA3 pyramidal cell dendrites, however, the dendritic region varied with sex. Additionally, acute THC also resulted in a sex-specific redistribution of DORs within CA3 pyramidal cell dendrites which could differentially promote synaptic plasticity and/or opioid-associated learning processes in both females and males.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.