Abstract
We report results in rats pretreated with (±)-zacopride (0.03 mg/kg, IP), ICS 205-930 (0.1 mg/kg, IP), and MDL 72222 (1.0 mg/kg, IP) 15 min before challenge with (-)-cocaine (10.0 mg/kg, IP). At a dose of 10 μg/kg, zacopride significantly inhibited (approximately 50%) cocaine-induced locomotion. We also investigated whether or not 5-hydroxytryptamine3 (5-HT3) antagonists block the cocaine binding site on the dopamine transporter and/or affect the ability of dopamine to regulate this binding site. In well-washed striatal membranes, neither zacopride nor ICS 205-930 (10-9-10-5 M) inhibited [3H]2β-carbomethoxy-3β-(4-fluorophenyl)tropane ([3H]WIN 35,428) (0.3 nM) binding. Furthermore, neither of these compounds affected the ability of dopamine to block WIN 35,428 binding. To determine if 5-HT is required for the 5-HT3 antagonist effect, we examined the interaction between cocaine and zacopride in rats pretreated with p-chlorophenylalanine (PCPA) (3 days × 100 mg/kg/day). PCPA pretreatment shifted the cocaine dose-response curve to the right and blocked the ability of zacopride to reverse cocaine-induced activity.
Original language | English (US) |
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Pages (from-to) | 871-879 |
Number of pages | 9 |
Journal | Pharmacology, Biochemistry and Behavior |
Volume | 43 |
Issue number | 3 |
DOIs | |
State | Published - Nov 1992 |
Externally published | Yes |
Keywords
- 5-HT antagonists
- Behavior
- Cocaine
- Dopamine transporter
- PCPA
- Rat
- Serotonin
ASJC Scopus subject areas
- Biochemistry
- Toxicology
- Pharmacology
- Clinical Biochemistry
- Biological Psychiatry
- Behavioral Neuroscience