Effect of MS-153, a glutamate transporter activator, on the conditioned rewarding effects of morphine, methamphetamine and cocaine in mice

Behav Brain Res. 2005 Jan 30;156(2):233-9. doi: 10.1016/j.bbr.2004.05.029.

Abstract

There is a body of evidence implying the involvement of the glutamatergic system in the conditioned rewarding effects of drugs of abuse. It is recognized that the release of extracellular glutamate from nerve terminals is counterbalanced by the functions of neuronal and glial glutamate transporters. In the present study, we investigated the effects of (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), a glutamate transporter activator, on the induction of the conditioned place preference to morphine, methamphetamine and cocaine in mice. In the conditioned place preference paradigm, mice were conditioned with repeated subcutaneous injections of morphine (5 mg/kg), methamphetamine (2 mg/kg) or cocaine (8 mg/kg) in combination with or without MS-153 (3 and 10 mg/kg). Co-administration of MS-153 at a dose of 10 mg/kg, but not 3 mg/kg, significantly attenuated the induction of conditioned place preference to morphine, methamphetamine and cocaine. However, MS-153 itself produced neither conditioned place preference nor aversion. On the other hand, co-administration of MS-153 (10 mg/kg) did not alter the acute locomotor activation elicited by a single injection of morphine, methamphetamine and cocaine. These results suggest that MS-153, a glutamate transporter activator, has an inhibitory effect on the conditioned rewarding effects of morphine, methamphetamine and cocaine without affecting their acute locomotor responses.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / metabolism*
  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Central Nervous System Stimulants / pharmacology
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Drug Interactions
  • Male
  • Methamphetamine / pharmacology*
  • Mice
  • Morphine / pharmacology*
  • Motor Activity / drug effects
  • Narcotics / pharmacology
  • Nicotinic Acids / pharmacology*
  • Reward*
  • Time Factors

Substances

  • 5-methyl-1-nicotinoyl-2-pyrazoline
  • Amino Acid Transport System X-AG
  • Central Nervous System Stimulants
  • Drug Combinations
  • Narcotics
  • Nicotinic Acids
  • Methamphetamine
  • Morphine
  • Cocaine