Details

Autor(en) / Beteiligte

• Tapia, Melissa A.
• Sage, Andrew S.
• Fullerton, Emma I.
• Judd, Jessica M.
• Hildebrant, Paige C.
• Will, Matthew J.
• Lever, Susan Z.
• Lever, John R.
• Miller, Dennis K.

Titel

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

Ist Teil von

• Psychopharmacology, 2020-03, Vol.237 (3), p.723-734

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2020

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• Rationale 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. Objectives 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. Results 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. Conclusion 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.