In vivo electrochemical assessment of dopamine release during conditioned withdrawal in heroin dependent rats

Abstract

The centers for disease control and prevention reports that heroin abuse has doubled for Americans aged 18–25. Drugs of abuse, such as heroin, are commonly thought to increase the concentration of dopamine (DA) in the nucleus accumbens core (NAcc), although their effects on phasic DA release events remains to be fully characterized. In contrast, when an addicted subject is withdrawn from a substance such as heroin, there is a clear suppression of phasic DA activity in the NAcc. Heroin withdrawal presents characteristic symptoms, most predominately increased craving for the drug, which contributes to further abuse. While withdrawal symptoms have been shown to be conditioned to previously neutral stimuli through classical conditioning, there is a lack of electrochemical evidence of conditioned withdrawal and its effects on non‐drug related stimuli. Here, we sought to explore how conditioned withdrawal in heroin addicted rats affects DA. We provided rats 23 hour access to IV heroin over 28 days. The 28 days are split into four blocks of increasing doses ranging from 0.06 mg/kg to 6 mg/kg to more accurately simulate the progression of heroin addiction. During the 28 day history, circadian changes in heroin, food, and water intake were altered and overall consumption of heroin increased. We then, investigated how conditioned withdrawal affects cue‐evoked dopamine release in the NAcc using fast scan cyclic voltammetry (FSCV) during conditioned suppression of food maintained responding. Here, animals were first trained to respond for food under an FR1 schedule for 3 consecutive days where food availability was predicted by a cue‐light placed above the lever. This was followed by 3 consecutive days of conditioned withdrawal training where a tone was conditioned to naloxone‐precipitated withdrawal. On test day, animals responded for food under normal conditions, but the withdrawal associated tone was presented concurrently with cue‐light onset during 50% of trials. By simultaneously presenting the withdrawal paired tone with the food predictive cue light we observed a substantial suppression of DA concentration at the cue light relative to non‐paired trials. These data demonstrated that conditioned suppression of food maintained responding induced by conditioned heroin withdrawal is accompanied by a transient suppression in dopamine concentrationSupport or Funding InformationFunding for the project was provided by NSF grant IOS‐1557755, NIH grant R03DA038734, Boettcher Young Investigator Award and NARSAD Young Investigator Award to EBO and an institutional UROP to KJP.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.