Cocaine self‐administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine
Year: 2015
Type: article
Abstract: Dopaminergic projections from the ventral midbrain to the nucleus accumbens (NAc) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine-induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self-administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NAc projection neurons. Over 5 days of cocaine self-administration (fixed-ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self-administration, there was a marked reduction in ventral tegmental area-stimulated NAc dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug-taking and drug-seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse.
Source: European Journal of Neuroscience
DOI: 10.1111/ejn.12970
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G1131764887, G1302830330, G1439428591, G1611948964, Center for the Neurobiology of Addiction Treatment, G475266968, Amphetamine administration during a rodent model of cocaine abuse, Methylphenidate, Serotonin and Dopamine Interactions, nAChR sensitivity and individual differences in drug abuse vulnerability, G7020460998, G9000006828, G9000076457, G9000155347, G9000156666, G9000198522, G9000269108, G9000353775, Multidisciplinary Training in the Biology of Alcohol Addiction
OpenAlex ID: W2134164757