Vaporized Cannabis Extracts Have Reinforcing Properties and Support Conditioned Drug-Seeking Behavior in Rats

This paper creates a good foundation in introducing the effects of vaporized cannabis on reinforcing drug-seeking behaviours. The authors focus on the motivational component of reward-oriented behaviours to habitual drug-seeking behaviours. The study introduces different fixed ratios to determine the effects of motivation, and their results demonstrate that effort influences increased self-administration of illicit drugs. However, motivation is only one aspect of this transition. Therefore, future studies should investigate the genomic changes, the second aspect of the transition from reward-oriented behaviours to habitual drug-seeking behaviours.

Investigating the effects of THC exposure on the genes Cnr1, Grin1, Gin2a, and Gria2 of the dorsal striatum will help consolidate the transition from reward-oriented behaviours to habitual drug-seeking behaviours. These mRNA levels, if affected by THC administration, will demonstrate the progression from recreational drug use to addiction disorder [4].

The Cnr1 gene encodes for the CB1 receptor, a direct target of THC, and is critical to forming striatal long-term depression (LTD) and synaptic plasticity [1] [2] [4]. The activity of the medium spiny neurons in the striatum regulates glutamatergic inputs and LTD [3]. Striatal LTD is closely associated with habitual behaviours and reinforcement learning [4] [5] [6]. With the investigation of Cnr1 and NMDA receptors in the striatum, you will be able to consolidate your findings and determine that THC affects the transition from reward-oriented to habitual compulsive drug-taking.

Reference
[1] Gerdeman GL, Ronesi J, Lovinger DM (2002). Postsynaptic endocannabinoid release is critical to long-term depression in the striatum. Nat Neurosci, 5, 446–451. doi:10.1038/nn832
[2] Gerdeman GL, Partridge JG, Lupica CR, Lovinger DM (2003). It could be habit forming: drugs of abuse and striatal synaptic plasticity. Trends in neurosciences, 26, 184–192. doi: 10.1016/S0166-2236(03)00065-1
[3] Grueter, B., Rothwell, P. and Malenka, R. (2012). Integrating synaptic plasticity and striatal circuit function in addiction. Current Opinion in Neurobiology, 22(3), 545-551. doi: 10.1016/j.conb.2011.09.009
[4] Szutorisz, H., Dinieri, J. A., Sweet, E., Egervari, G., Michaelides, M., Carter, J. M., . . . Hurd, Y. L. (2014). Parental THC Exposure Leads to Compulsive Heroin-Seeking and Altered Striatal Synaptic Plasticity in the Subsequent Generation. Neuropsychopharmacology, 39(6), 1315-1323. doi: 10.1038/npp.2013.352
[5] Szutorisz, H., Egervári, G., Sperry, J., Carter, J. and Hurd, Y. (2016). Cross-generational THC exposure alters the developmental sensitivity of ventral and dorsal striatal gene expression in male and female offspring. Neurotoxicology and Teratology, 58, 107-114. doi: 10.1016/j.ntt.2016.05.005
[6] Yager, L., Garcia, A., Wunsch, A., & Ferguson, S. (2015). The ins and outs of the striatum: Role in drug addiction. Neuroscience, 301, 529-541. doi: 10.1016/j.neuroscience.2015.06.033