Characterization of Polysubstance Use: Combined Fentanyl and Methamphetamine

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Project Summary The opioid epidemic currently affecting the United States has entered a new wave of mortality, with combined use of opioid and psychomotor simulants as a major contributing factor to the number of overdose deaths. Combined use of fentanyl and methamphetamine may be due to a number of factors, including greater rewarding effects, decreased negative side effects, and/or feelings that combined use is somehow ‘safer’ than use of fentanyl alone. For those reasons, there is a clear need to examine the differences in the behavioral and neurobiological alterations that occur following chronic use of fentanyl, methamphetamine, and these two substances in combination. My preliminary findings suggest that there is enhanced hypodopaminergia following combined use of fentanyl and methamphetamine (COMBO) when compared to fentanyl use alone. I have determined that 1) in both male and female rats, elicited DA release was decreased in COMBO animals compared to fentanyl alone animals and; (2) male COMBO animals had greater response rates and responded more on a progressive ratio schedule of reinforcement. Therefore, this study aims to investigate the scarcely studied combination of fentanyl and methamphetamine via a three-pronged approach examining behavioral and neurobiological alterations to the DA system through self-administration, microdialysis and fast scan cyclic voltammetry, and the use of the novel photosensor dLight during behavioral responding. Collectively, the proposed aims will provide insight into the neurobiological and behavioral differences elicited by combined use of fentanyl and methamphetamine, an under-studied topic that is highly relevant for the current state of the opioid epidemic in the United States.