Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats.
Linyuan Shi, Shuo Kang, Chan Young Choi, Brynn L Noonan, Lauren K Carrica, Nu-Chu Liang, Joshua M Gulley
Neuropharmacology January 1, 2024 DOI: 10.1016/j.neuropharm.2023.109765 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male and female Long-Evans rats exposed to drugs during adolescence (postnatal days 30-45) |
| Interventions | Delta-9-tetrahydrocannabinol (THC) Ethanol Indiplon AR-A014418 |
| Dose | THC escalating doses, 3-20 mg/kg; 10% ethanol |
| Duration | Daily injections from postnatal days 30-45; recordings after 3-4 weeks of abstinence |
| Topics | Cannabis Neuroplasticity |
| Keywords | Adolescence Delta-9-tetrahydrocannabinol Ethanol Gaba Plasticity Polydrug use Prelimbic cortex |
| Key findings | Adolescent exposure to THC or ethanol alone reduced high-frequency stimulation-induced LTD in the prelimbic cortex, and combined exposure abolished LTD after 3-4 weeks of abstinence. Indiplon and AR-A014418 responses suggested the effects were due in part to lasting adaptations in GABA and GSK3β signaling. |
Abstract
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.
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Citations in the library
Cites 6
- Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users Psychopharmacology October 30, 2010
- Adolescent exposure to delta-9-tetrahydrocannabinol and ethanol heightens sensitivity to fear stimuli. Behavioural Brain Research October 11, 2021
- Adolescent exposure to THC in female rats disrupts developmental changes in the prefrontal cortex. Neurobiology of Disease 2015
- Effects of ethanol, Δ(9)-tetrahydrocannabinol, or their combination on object recognition memory and object preference in adolescent and adult male rats. Neuroscience Letters October 3, 2012
- Chronic delta 9-tetrahydrocannabinol during adolescence provokes sex-dependent changes in the emotional profile in adult rats: behavioral and biochemical correlates. Neuropsychopharmacology October 2008
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