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U-69593 prevents cocaine sensitization by normalizing basal accumbens dopamine
C A Heidbreder1, T S Shippenberg
1National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Neuroreport
|September 8, 1994
Summary
Repeated cocaine use increases dopamine in the brain, leading to heightened responses. A kappa-opioid receptor agonist, U-69593, prevented these cocaine-induced effects, suggesting a way to block drug sensitization.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Repeated cocaine administration can alter dopamine (DA) signaling in the brain's reward pathways.
- This can lead to behavioral sensitization, where the drug's effects become amplified with subsequent exposures.
Purpose of the Study:
- To investigate the effect of a selective kappa-opioid receptor agonist (U-69593) on cocaine-induced dopamine overflow and behavioral sensitization.
- To explore the relationship between basal dopamine levels in the nucleus accumbens (ACB) and the development of cocaine sensitization.
Main Methods:
- Rats were administered cocaine intermittently over 3 days.
- Dopamine overflow in the nucleus accumbens was measured 48 hours post-treatment.
- Behavioral responses (stereotypy) to a cocaine challenge were assessed.
- U-69593 was co-administered with cocaine in some groups.
Main Results:
- Cocaine treatment significantly increased basal dopamine overflow in the ACB and enhanced behavioral responses to a subsequent cocaine challenge.
- Co-administration of U-69593 with cocaine abolished these cocaine-induced increases in dopamine and behavioral sensitization.
Conclusions:
- Basal dopamine levels in the nucleus accumbens are closely linked to the mesolimbic dopamine system's response to cocaine.
- U-69593 may prevent cocaine-induced behavioral sensitization by normalizing elevated basal dopamine levels.