Dopamine D1-Like Receptor Agonist and D2-Like Receptor Antagonist (-)-Stepholidine Reduces Reinstatement of Drug-Seeking Behavior for 3,4-Methylenedioxypyrovalerone (MDPV) in Rats
| Autor: | Garry R. Smith, Sunil U. Nayak, Peng Huang, Yohanka Caro, Scott M. Rawls, Linnet Ramos, Allen B. Reitz, David Y.W. Lee, Lee-Yuan Liu-Chen, Callum Hicks |
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| Rok vydání: | 2018 |
| Předmět: |
Agonist
Pyrrolidines Berberine Physiology medicine.drug_class Cognitive Neuroscience Stepholidine Drug-Seeking Behavior D1-like receptor Pharmacology Biochemistry Article Extinction Psychological Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cocaine mental disorders medicine Animals Humans Benzodioxoles Behavior Animal Chemistry Receptors Dopamine D1 Cell Biology General Medicine Receptor antagonist Synthetic Cathinone Conditioned place preference 030227 psychiatry Dopamine receptor D2-like receptor Dopamine Agonists Dopamine Antagonists Self-administration 030217 neurology & neurosurgery |
| Zdroj: | ACS chemical neuroscience. 9(6) |
| ISSN: | 1948-7193 |
| Popis: | Psychostimulant reinforcement is mediated by stimulation of both dopamine (DA) D1-like and D2-like receptors, suggesting that pharmacotherapy agents with a dual DA receptor mechanism may be useful for managing psychostimulant abuse. (-)-Stepholidine (L-SPD) is a Chinese herbal extract that functions as a D1-like receptor agonist and D2-like receptor antagonist. L-SPD has been shown to attenuate the reinforcing effects of heroin; however, its effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. The current study determined the effects of L-SPD on reinstatement of MDPV-seeking behavior in the drug intravenous self-administration (IVSA) and conditioned place preference (CPP) paradigms. To determine whether the effects of L-SPD were specific to psychostimulant reinforcement, we also examined its effects on sucrose-seeking behavior. Using a locomotor activity assay, we tested the locomotor effects of L-SPD, as well as its effects on MDPV-induced hyperactivity. The results of a battery of in vitro binding and functional assays confirmed that L-SPD functioned as a D1-like receptor agonist and D2-like receptor antagonist. In behavioral experiments, L-SPD dose-dependently attenuated cue plus MDPV-primed reinstatement of MDPV-seeking behavior in the IVSA model. The highest dose of L-SPD also attenuated MDPV-primed reinstatement of MDPV CPP, as well as cue-induced reinstatement of sucrose-seeking. L-SPD had no significant locomotor effects, and did not modulate the robust hyperactivity induced by MDPV. The current findings show for the first time a robust reinstatement effect with MDPV, which can be reduced by L-SPD. These results establish a role for DA receptors in drug-seeking behavior for MDPV. |
| Databáze: | OpenAIRE |
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