The Relationship between Vaping Cannabis and Frequency of Cannabis Use and Cannabis-Related Problems among Urban High School Students.

Drugs of abuse share an ability to enhance dopamine (DA) transmission in the mesocorticolimbic system, an interconnected network of brain regions including the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) that mediates the processing and learning related to rewarding stimuli. DA neurons of the ventral tegmental area (VTA) are an integral component of the mesocorticolimbic system. Optogenetic manipulation of VTA DA neurons is a powerful means to assess the contribution of these neurons to reward-related behavior. For example, optogenetic stimulation of VTA DA neurons enhances locomotor activity in mice, mimicking the unconditioned DA-dependent response evoked by drugs of abuse. Optogenetic stimulation of VTA DA neurons can also induce a conditioned place preference. Studies employing optogenetic tools have shown that rodents will engage in instrumental responding to self-stimulate VTA DA neurons. Optical self-stimulation (OSS) of VTA DA neurons allows for response-contingent activation of VTA DA neurons, mimicking the ability of addictive drugs to enhance DA transmission in the mesocorticolimbic system. OSS of VTA DA neurons is sufficient to induce key cellular and behavioral hallmarks of repeated drug exposure in mice, including potentiation of glutamatergic neurotransmission in the NAc and resistance of reward-seeking behavior to punishment. OSS has also highlighted critical roles of discrete VTA DA neuron projections in reinforcement and cue-induced reinstatement of reward-seeking behavior. Genetic manipulation of VTA DA neurons in support of OSS and other addiction-relevant paradigms generally involves a transgenic rodent line expressing Cre recombinase under the control of the promoter for tyrosine hydroxylase (TH) or the DA transporter (DAT), together with intra-VTA infusion of a Cre-dependent adeno-associated virus (AAV) vector. Reliance on transgenic Cre driver lines for studies of VTA DA neurons limits investigations to genetically tractable species and comes with the associated costs of acquiring, maintaining, and genotyping mutant strains. In-house breeding capacity is a rate-limiting factor in these studies, and study costs and delays are compounded if breeding the Cre driver line with a different inbred strain or mutant strain (e.g., a knockout line) is desired.