The sigma receptor ligand N-phenylpropyl-N'-(4-methoxyphenethyl)3piperazine (YZ-067) enhances the cocaine conditioned-rewarding properties while inhibiting the development of sensitization of cocaine in mice
| Autor: | Dennis K. Miller, John R. Lever, Emma I. Fullerton, Melissa A. Tapia, Paige C. Hildebrant, Matthew J. Will, Susan Z. Lever, Andrew S. Sage, Jessica M. Judd |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Sigma receptor Pharmacology Piperazines 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cocaine Dopamine Uptake Inhibitors Reward Conditioning Psychological medicine Animals Receptors sigma Receptor Sensitization Dose-Response Relationship Drug Ligand (biochemistry) Zero maze Conditioned place preference 030227 psychiatry Piperazine Locomotor sensitization medicine.anatomical_structure chemistry 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Psychopharmacology. 237(3) |
| ISSN: | 1432-2072 |
| Popis: | The N-phenylpropyl-N′-substituted piperazines SA-4503 (N-phenylpropyl-N′-(3,4-dimethoxyphenethyl)piperazine) and YZ-185 (N-phenylpropyl-N′-(3-methoxyphenethyl)piperazine) bind to sigma (σ) receptors and block the development of cocaine-induced conditioned place preference at concentrations that inhibit cocaine-induced hyperactivity. YZ-067 (N-phenylpropyl-N′-(4-methoxyphenethyl)piperazine) also binds to sigma receptors and attenuates cocaine-induced hyperactivity in mice. The present study determined the effect of YZ-067 on the development and expression of cocaine (66 μmol/kg or 33 μmol/kg) conditioned place preference (CPP) and locomotor sensitization in mice. YZ-067 (10 or 31.6 μmol/kg) did not have intrinsic effects on place preference or place aversion. Interestingly, the 31.6 μmol/kg YZ-067 dose enhanced the development of cocaine place preference, while 10 μmol/kg YZ-067 attenuated the development of cocaine-induced locomotor sensitization. However, YZ-067 did not alter the expression of cocaine place preference nor cocaine-induced locomotor sensitization. In follow-up studies, YZ-067 did not affect performance in the zero maze or rotarod, indicating that sigma receptors probed by this ligand do not regulate anxiety-like or coordinated motor skill behaviors, respectively. Overall, these results are consistent with previous studies demonstrating a role for sigma receptors in the behavioral effects of cocaine. However, the present findings also indicate that N-phenylpropyl-N′-substituted piperazines do not strictly block cocaine’s behavioral effects and that sigma receptor may differentially mediate cocaine-induced hyperactivity and place conditioning. |
| Databáze: | OpenAIRE |
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