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Delta‐9‐tetrahydrocannabinol potentiates fear memory salience through functional modulation of mesolimbic dopaminergic activity states
Author(s) -
Fitoussi Aurelie,
Zunder Jordan,
Tan Huibing,
Laviolette Steven R.
Publication year - 2018
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13951
Subject(s) - ventral tegmental area , nucleus accumbens , neuroscience , psychology , dopaminergic , dopamine , mesolimbic pathway
Chronic or acute exposure to delta‐9‐tetrahydrocannabinol ( THC ), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side‐effects, including dysregulation of emotional processing and associative memory formation. Clinical and preclinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine ( DA ) activity states in the nucleus accumbens ( NA c) and ventral tegmental area ( VTA ). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood. Using an olfactory associative fear memory procedure combined with in vivo neuronal electrophysiology, we examined the effects of direct THC microinfusions targeting the shell region of the NA c ( NAS h) and examined how THC may modulate the processing of fear‐related emotional memory and concomitant activity states of the mesolimbic DA system. We report that intra‐ NAS h THC dose‐dependently potentiates the emotional salience of normally subthreshold fear conditioning cues. These effects were dependent upon intra‐ VTA transmission through GABA ergic receptor mechanisms and intra‐ NAS h DA ergic transmission. Furthermore, doses of intra‐ NAS h THC that potentiated fear memory salience were found to modulate intra‐ VTA neuronal network activity by increasing the spontaneous firing and bursting frequency of DA ergic neurones whilst decreasing the activity levels of a subpopulation of putative GABA ergic VTA neurones. These findings demonstrate that THC can act directly in the NAS h to modulate mesolimbic activity states and induce disturbances in emotional salience and memory formation through modulation of VTA DA ergic transmission.