Details

Autor(en) / Beteiligte

• Shi, Linyuan
• Kang, Shuo
• Choi, Chan Young
• Noonan, Brynn L.
• Carrica, Lauren K.
• Liang, Nu-Chu
• Gulley, Joshua M.

Titel

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

Ist Teil von

• Neuropharmacology, 2024-01, Vol.242, p.109765-109765, Article 109765

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Significant exposure to alcohol or cannabis during adolescence can induce lasting disruptions of neuronal signaling in brain regions that are later to mature, such as the medial prefrontal cortex (mPFC). Considerably less is known about the effects of alcohol and cannabis co-use, despite its common occurrence. Here, we used male and female Long-Evans rats to investigate the effects of early-life exposure to ethanol, delta-9-tetrahydrocannabinol (THC), or their combination on high frequency stimulation (HFS)-induced plasticity in the prelimbic region of the mPFC. Animals were injected daily from postnatal days 30–45 with vehicle or THC (escalating doses, 3–20 mg/kg) and allowed to drink vehicle (0.1% saccharin) or 10% ethanol immediately after each injection. In vitro brain slice electrophysiology was then used to record population responses of layer V neurons following HFS in layer II/III after 3–4 weeks of abstinence. We found that THC exposure reduced body weight gains observed in ad libitum fed rats, and reduced intake of saccharin and ethanol. Compared to controls, there was a significant reduction in HFS-induced long-term depression (LTD) in rats exposed to either drug alone, and an absence of LTD in rats exposed to the drug combination. Bath application of indiplon or AR-A014418, which enhance GABAA receptor function or inhibit glycogen synthase kinase 3β (GSK3β), respectively, suggested the effects of ethanol, THC or their combination were due in part to lasting adaptations in GABA and GSK3β signaling. These results suggest the potential for long-lasting adaptations in mPFC output following co-exposure to alcohol and THC. •Daily THC injection reduced body weight gains, intake of saccharin and ethanol.•Adolescent exposure to ethanol and THC impaired plasticity in prelimbic cortex.•This plasticity was restored with perfusion of GABA PAM and GSK3β inhibitor.