Abstract
This study was conducted to determine whether dopamine (DA) release in the nucleus accumbens (NACC) following 5-HT(2A) receptor stimulation is potentiated by intermittent cocaine. Rats received daily injections of either saline or cocaine (30 mg/kg, s.c.) for 14 days. At the 7th day after withdrawal, microdialysis was performed in the NACC. Infusion of (+/-)-1-(4-iodo-2, 5-dimethoxyphenyl)-2-aminopropane (DOI, 50 microM), a 5-HT(2) receptor agonist, into the NACC produced greater and longer-lasting increases in extracellular DA in the rats pretreated with cocaine than in the rats pretreated with saline. The DOI-induced increases in NACC DA were attenuated by co-perfusion with ketanserin (50 microM), a 5-HT(2A) receptor antagonist. The results are consistent with the concept that intermittent cocaine may cause enhanced sensitivity of 5-HT(2A) receptors within the NACC.
MeSH terms
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Amphetamines / pharmacology
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Animals
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Cocaine / pharmacology*
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Cocaine-Related Disorders / physiopathology
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Dopamine / metabolism*
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Dopamine Uptake Inhibitors / pharmacology*
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Drug Administration Schedule*
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Ketanserin / pharmacology
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Male
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Microdialysis
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism*
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Nucleus Accumbens / cytology
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / metabolism*
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Rats
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Rats, Sprague-Dawley
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / pharmacology
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Serotonin Receptor Agonists / pharmacology
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Substance Withdrawal Syndrome / physiopathology
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Time Factors
Substances
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Amphetamines
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Dopamine Uptake Inhibitors
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Receptor, Serotonin, 5-HT2A
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Receptors, Serotonin
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Serotonin Antagonists
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Serotonin Receptor Agonists
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Ketanserin
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Cocaine
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4-iodo-2,5-dimethoxyphenylisopropylamine
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Dopamine