Dissociable roles of dopamine within the core and medial shell of the nucleus accumbens in memory for objects and place.
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ABSTRACT:
SUBMITTER: Nelson AJ
PROVIDER: S-EPMC3002220 | biostudies-other | 2010 Dec
REPOSITORIES: biostudies-other
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Project description:The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.
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Project description:BackgroundTraumatic brain injury is known to impact dopamine-mediated reward pathways, but the underlying mechanisms have not been fully established.MethodsNicotine-induced conditional place preference was used to study rats exposed to a 6-psi fluid percussion injury with and without prior exposure to nicotine. Preference was quantified as a score defined as (C1 - C2) / (C1 + C2), where C1 is time in the nicotine-paired compartment and C2 is time in the saline-paired compartment. Subsequent fast-scan cyclic voltammetry was used to analyze the impact of nicotine infusion on dopamine release in the shell portion of the nucleus accumbens. To further determine the influence of brain injury on nicotine withdrawal, nicotine infusion was administered to the rats after fluid percussion injury. The effects of fluid percussion injury on conditional place preference after prior exposure to nicotine and abstinence or withdrawal from nicotine were also assessed.ResultsAfter traumatic brain injury, dopamine release was reduced in the nucleus accumbens shell, and nicotine-induced conditional place preference preference was significantly impaired. Preference scores of control, sham-injured, and fluid percussion injury groups were 0.1627±0.04204, 0.1515±0.03806, and -0.001300±0.04286, respectively. Nicotine-induced conditional place preference was also seen in animals after nicotine pretreatment, with a conditional place preference score of 0.07805±0.02838. Nicotine preexposure substantially increased tonic dopamine release in sham-injured animals, but it did not change phasic release; nicotine exposure after fluid percussion injury enhanced phasic release, though not to the same levels seen in sham-injured rats. Conditioned preference was related not only to phasic dopamine release (r=0.8110) but also to the difference between tonic and phasic dopamine levels (r=0.9521).ConclusionsTraumatic brain injury suppresses dopamine release from the shell portion of the nucleus accumbens, which in turn significantly alters reward-seeking behavior. These results have important implications for tobacco and drug use after traumatic brain injury.
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