Abstract
The purpose of this study was to examine whether blockade of either dopamine D1-like or D2-like receptors by selective antagonist administration into the nucleus accumbens (NAc) is sufficient to reverse cocaine-induced locomotion, and to develop a new technique that enables the population of receptors occupied by the antagonists to be quantified. Locomotor activity was assessed in rats that had received bilateral intra-accumbens injections of the D1-selective antagonist SCH-23390 (0-3.0 μg/0.5 μl/side) or the D2/D3-selective antagonist sulpiride (0-1.0 μg/0.5 μl/side), followed 15 min later by injections of saline or cocaine (15 mg/kg, i.p.). To assess receptor occupancy by the antagonists, 105 min prior to sacrifice the rats received intra-accumbens injections of the antagonist, followed 15 min later by an injection of the non-selective irreversible antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ; 10 mg/kg, i.p.). Receptors were labeled with [3H]SCH-23390 or [3H]sulpiride in sections containing the NAc, and the autoradiograms allowed quantitation of receptors occupied (i.e. protected from EEDQ) by the antagonist given in vivo. Only a dose of 3 μg/side SCH-23390 reversed cocaine-induced locomotion, whereas a dose of 0.5 μg/side did not alter cocaine-induced locomotion despite occupying the same amount of [3H]SCH-23390 binding sites in the NAc. Intermediate doses of 0.1 and 0.3 μg/side sulpiride reversed cocaine-induced locomotion, and also occupied the greatest number of [3H]sulpiride binding sites in the NAc. The results suggest that blockade of D2-like, but not D1-like, receptors in the NAc is sufficient to reverse cocaine-induced locomotion, and also demonstrate the importance of quantifying receptors occupied by drugs administered intracranially.
Original language | English (US) |
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Pages (from-to) | 201-212 |
Number of pages | 12 |
Journal | Brain Research |
Volume | 671 |
Issue number | 2 |
DOIs | |
State | Published - Feb 13 1995 |
Keywords
- Cocaine
- D1-like
- D2-like
- Dopamine receptor
- Locomotor activity
- N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline
- Nucleus accumbens
- Receptor occupancy
- SCH-23390
- Stereotypy
- Sulpiride
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology