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Differential Effects of δ‐ and μ‐Opioid Receptor Antagonists on the Amphetamine‐Induced Increase in Extracellular Dopamine in Striatum and Nucleus Accumbens
Author(s) -
Schad Christina A.,
Justice Joseph B.,
Holtzman Stephen G.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062292.x
Subject(s) - naltrindole , nucleus accumbens , amphetamine , dopamine , striatum , chemistry , neurochemical , opioid receptor , opioid , pharmacology , medicine , endocrinology , dopamine receptor d1 , opioid antagonist , dopamine receptor , (+) naloxone , receptor , biochemistry
The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine‐induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective δ‐opioid receptor antagonist, but not by the irreversible μ‐opioid receptor antagonist β‐funaltrexamine. Therefore, this research was designed to determine if naltrindole would attenuate the neurochemical response to amphetamine as it did the behavioral response. In vivo microdialysis was used to monitor the change in extracellular concentrations of dopamine in awake rats. Naltrindole (3.0, 10, or 30 µg) or vehicle was given 15 min before and β‐funaltrexamine (10 µg) or vehicle 24 h before the start of cumulative dosing, intracisternally in a 10‐µl volume, while the rats were lightly anesthetized with methoxyflurane. Cumulative doses of subcutaneous d ‐amphetamine (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) followed pretreatment injections at 30‐min intervals. Dialysate samples were collected every 10 min from either the striatum or nucleus accumbens and analyzed for dopamine content by HPLC. Amphetamine dose‐dependently increased dopamine content in both the striatum and nucleus accumbens, as reported previously. Naltrindole (3.0, 10, and 30 µg) significantly reduced the dopamine response to amphetamine in the striatum. In contrast, 30 µg of naltrindole did not modify the dopamine response to amphetamine in the nucleus accumbens. On the other hand, β‐funaltrexamine (10 µg) had no effect in the striatum but significantly attenuated the amphetamine‐induced increase in extracellular dopamine content in the nucleus accumbens. These data suggest that δ‐opioid receptors play a relatively larger role than μ‐opioid receptors in mediating the amphetamine‐induced increase in extracellular dopamine content in the striatum, whereas μ‐opioid receptors play a larger role in mediating these effects in the nucleus accumbens.