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

Abstract

Derivatives from the Cannabis plant are the most commonly abused illegal substances in the world. The main psychoactive component found in the plant, Δ-9-tetrahydrocannabinol (THC), exerts its effects through the endocannabinoid system. Manipulations of this system affect some types of learning that seem to be dependent on dorsal striatum synaptic plasticity. Dendritic spines exhibit important synaptic functional attributes and a potential for plasticity, which is thought to mediate long-lasting changes in behaviour. To study the possible structural plasticity changes that prolonged THC administration might exert in the dorsal striatum, adult, male C57BL6/J mice were intraperitoneally injected with THC (10mg/kg) or vehicle for 15 days followed by a 7-day drug-free period. Using single cell intracellular injections of Lucifer Yellow, confocal microscopy, and 3D reconstruction of labelled neurons, we studied dendritic spine density and spine size in medium spiny neurons (MSNs) of the anterior dorsolateral striatum (aDLS) and posterior dorsomedial striatum (pDMS). We found that the THC treatment increased dendritic spine density in the distal part of the dendrites of MSNs in the pDMS, but no changes were found in the rest of the parameters analysed in either region studied. We also observed that dendritic spines of MSNs of pDMS presented lower volume and surface area values than MSNs of the aDLS. These results seem to indicate that THC could induce structural plasticity alterations in the circuits involving pDMS MSNs.

Testing the Role of Δ9-Tetrahydrocannabinol During Adolescence as a Gateway Drug: Behavioural, Brain Imaging and Transcriptomic Studies

“…This is interesting in the general context of the involvement of the endocannabinoid systems in habit formation (60–62). We and others have shown that a regime of THC exposure in adult animals accelerated habit formation (62, 63) and, we also found that the THC treatment increased dendritic spine density in the distal part of the dendrites of medium spiny neurons in the posterior dorsomedial striatum (64) suggesting a potential mechanism of these alterations in the balance between goal-directed behaviour and habits. However, when the treatment occurred during adolescence, we observed no such behavioural effects.…”

Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

“…The persistent licking during the inter-food interval seen in the animals treated with THC may reflect some features of habit-like behaviours. In this regard, cannabinoids influence the transition from volitional behaviour to habit formation, and chronic exposure to them induces structural plasticity in the dorsal striatum, a region closely involved in this kind of behaviour (Fernandez-Cabrera et al 2018;Goodman and Packard 2015;Lovinger et al 2010). Recent research has demonstrated that rats subjected to the SID model exhibited greater habitual-like behaviour (Merchán et al 2019).…”

CB1 Activity Drives the Selection of Navigational Strategies: A Behavioral and c-Fos Immunoreactivity Study

“…This observation fits the effects of AM251 treatment on DMS found in the present research, and makes us consider DMS as the crucial structure that may provide information about the role of CB 1 in the selection between navigational strategies. In fact, the multi-pronged observations that the manipulations on CB 1 activity modified DMS spine density [82], brought about changes in navigational behaviors (present findings, [41]), modulated c-Fos activation in DMS (present findings), are related to the presence of presynaptic CB 1 receptors (which is known to inhibit the neurotransmitter release) in both cortical glutamatergic afferents on and GABAergic terminals in MSN and in aspiny interneurons of dorsal striatum [83,84]. Furthermore, the present data indicate that to select more frequently the navigational strategy related to cognitive map it is required the full functionality of DMS neurons.…”