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Sigma-1 receptor ligand PD144418 and sigma-2 receptor ligand YUN-252 attenuate the stimulant effects of methamphetamine in mice.
Tapia, Melissa A; Lever, John R; Lever, Susan Z; Will, Matthew J; Park, Eric S; Miller, Dennis K.
Afiliação
  • Tapia MA; Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO, 65211, USA. matb6b@mail.missouri.edu.
  • Lever JR; Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, and Department of Radiology and Radiopharmaceutical Sciences Institute, University of Missouri, Columbia, MO, 65211, USA.
  • Lever SZ; Department of Chemistry and MU Research Reactor Center, University of Missouri, Columbia, MO, 65211, USA.
  • Will MJ; Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO, 65211, USA.
  • Park ES; Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO, 65211, USA.
  • Miller DK; Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO, 65211, USA.
Psychopharmacology (Berl) ; 236(11): 3147-3158, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31139878
ABSTRACT
RATIONALE Previous research indicates that the selective sigma-1 receptor ligand PD144418 and the selective sigma-2 ligands YUN-252 can inhibit cocaine-induced hyperactivity. The effects of these ligands on other stimulants, such as methamphetamine, have not been reported.

OBJECTIVES:

The present study examined the effects of PD144418 and YUN-252 pretreatment on methamphetamine-induced hyperactivity after acute treatment.

METHODS:

Mice (n = 8-14/group) were injected with PD144418 (3.16, 10, or 31.6 µmol/kg), YUN-252 (0.316, 3.16, 31.6 µmol/kg), or saline. After 15 min, mice injected with 2.69 µmol/kg methamphetamine or saline vehicle, where distance traveled during a 60-min period was recorded. Additionally, the effect of PD144418 on the initiation and expression of methamphetamine sensitization was determined by treating mice (n = 8-14/group) with PD144418, methamphetamine or saline repeatedly over a 5-day period, and testing said mice with a challenge dose after a 7-day withdrawal period.

RESULTS:

Results indicate that both PD144418 and YUN-252, in a dose-dependent manner, attenuated hyperactivity induced by an acute methamphetamine injection. Specifically, 10 µmol/kg or 31.6 µmol/kg of PD144418 and 31 µmol/kg of YUN-252 suppressed methamphetamine-induced hyperactivity. In regard to methamphetamine sensitization, while 10 µmol/kg PD144418 prevented the initiation of methamphetamine sensitization, it did not have an effect on the expression.

CONCLUSIONS:

Overall, the current results suggest an intriguing potential for this novel sigma receptor ligand as a treatment for the addictive properties of methamphetamine. Future analysis of this novel sigma receptor ligand in assays directly measuring reinforcement properties will be critical.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piridinas / Receptores sigma / Estimulantes do Sistema Nervoso Central / Isoxazóis / Locomoção / Metanfetamina Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piridinas / Receptores sigma / Estimulantes do Sistema Nervoso Central / Isoxazóis / Locomoção / Metanfetamina Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article