Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.
Maricela X. Martinez, Vanessa Alizo Vera, Christina M. Ruiz, Stan B Floresco, Stephen V Mahler
Psychopharmacology February 1, 2025 DOI: 10.1007/s00213-024-06676-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adult Long Evans rats treated with THC during adolescence |
| Interventions | THC amphetamine |
| Dose | 5 mg/kg THC daily for 14 days; amphetamine 0, 0.25, 0.5 mg/kg |
| Duration | 14 daily THC injections during adolescence; acute amphetamine or chemogenetic stimulation during probabilistic discounting in adulthood |
| Topics | Cannabis |
| Keywords | Chemogenetics Cognition Dopamine Medial prefrontal cortex Ventral tegmental area |
| Citations | 1 |
| Key findings | Adolescent THC exposure sex-dependently impacts acquisition of cue-guided reward seeking but has minimal effects on set-shifting or probabilistic discounting, and increases sensitivity to amphetamine-induced reduction of discounting of improbable rewards. |
Abstract
Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. We determined how 14 daily THC injections (5 mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition. In adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks-strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5 mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impact probabilistic discounting. AdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats. These studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.