Abstract
Chronic opiate exposure induces neuroadaptations in the mesocorticolimbic system including ventral tegmental area (VTA) dopamine (DA) neurons, whose soma size is decreased following opiate exposure. Yet it is now well documented that VTA DA neurons are heterogeneous, with notable differences between VTA DA neurons based on their projection target. Therefore, we sought to determine whether chronic morphine induced similar changes in the morphology of VTA DA neurons that project to the nucleus accumbens (NAc) and prefrontal cortex (PFC). We utilized Cre-dependent retrograde viral vectors in DA Cre driver lines to label VTA DA neurons that projected to NAc and PFC and assessed neuronal soma size. Consistent with previous data, the soma size of VTA DA neurons that projected to the NAc medial shell was decreased following morphine exposure. However, soma size of VTA DA neurons that projected to the NAc core was unaltered by morphine. Interestingly, morphology of PFC-projecting VTA DA neurons was also altered by morphine, but in this case soma size was increased compared to sham controls. Differences in basal soma size were also noted, suggesting stable differences in projection-specific morphology in addition to drug-induced changes. Together, these data suggest morphine-induced changes in VTA DA morphology occur within distinct VTA DA populations and that study of opiate-induced structural plasticity of individual VTA DA subcircuits may be critical for understanding addiction-related behavior.
Highlights
There is increasing concern in both the scientific and public domains regarding the United States opioid epidemic, highlighted by a 500% increase in opioid overdose deaths from 1999 to 2016 [5]
Since ventral tegmental area (VTA) DA neurons in tyrosine hydroxylase (TH)-Cre and DAT-Cre mice were similar in size, a single model (TH-Cre) was used in subsequent morphine studies and distinct subregions were analyzed separately in order to avoid any confounds of basal differences in soma size
We found no significant difference between the soma size of VTA DA neurons (PN subregion) of male and female DA-Cre mice (Fig. 1e, student t-test, t(13) = 0.007953, p = 0.99) consistent with observations that there are no sex differences in the basal electrophysiological properties, connectome or translatome of VTA DA neurons [10]
Summary
There is increasing concern in both the scientific and public domains regarding the United States opioid epidemic, highlighted by a 500% increase in opioid overdose deaths from 1999 to 2016 [5]. Following chronic morphine administration VTA DA neurons exhibit increased spontaneous and burst firing rates [23, 33] and a unique morphological adaptation, an ~ 20–25% reduction in soma size [9, 33, 41, 43]. Given that this reduction can be blocked with opiate antagonists such as naltrexone [43] and that it does not occur following chronic administration of other commonly abused drugs such as cocaine, ethanol, or nicotine [32] suggests that this structural plasticity may be dependent on opioid signaling. Decreased VTA DA soma size has been observed in post-mortem samples from heroin addicts, demonstrating translational relevance [33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
