THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity

Abstract

Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug.

Dopamine and addiction: what have we learned from 40 years of research

“…Chronic cocaine administration also increased spine density in the PFC, a brain area also targeted by DA neurons from the VTA (Robinson and Kolb 2004). Similar increases have also been described in response to nicotine (Brown and Kolb 2001), MDMA (Ball et al 2009), methamphetamine (Jedynak et al 2007) and THC (Kolb et al 2018). On the contrary, chronic alcohol (Zhou et al 2007) and morphine (Robinson and Kolb 1999), decrease the spine density in the NAc.…”

Selective effects of Δ9-tetrahydrocannabinol on medium spiny neurons in the striatum

“…Considering all these pieces of evidence, we suggest that the changes that we have observed may emerge soon after the treatment and they would be long lasting. Indeed, it was previously reported that chronic exposure to THC modified the structure of the dendrites in the Nacc shell and the mPFC one month after THC cessation with lower doses than in the present study [ 34 ], and a more recent study reports that changes in spine density endures for 90 days in these regions [ 73 ].…”

Cannabis Addiction and the Brain: a Review

“…Future research should also consider whether THC’s effects on neurons and microglia are related to addiction. Previous research indicates that chronic THC exposure in animals seems to activate microglia and produce neuroinflammation that may underlie some of the cognitive deficits associated with CUD (Melis et al 2017 ); additionally, changes in neuron and glia morphology after chronic cannabis exposure may also contribute to the persistent cognitive and behavioral deficits linked to CUD (Cutando et al 2013 ; Kolb et al 2018 ). Therefore, future studies should investigate whether chronic THC exposure in animals and humans is linked to changes in various cell types in the brain that contribute to cannabis addiction through neuroinflammation.…”