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AMPA antagonist LY293558 blocks the development, without blocking the expression, of behavioral sensitization to morphine.

Authors
  • Carlezon, W A Jr
  • Rasmussen, K
  • Nestler, E J
Type
Published Article
Journal
Synapse (New York, N.Y.)
Publication Date
Mar 15, 1999
Volume
31
Issue
4
Pages
256–262
Identifiers
PMID: 10051106
Source
Medline
License
Unknown

Abstract

Morphine (3.0 mg/kg, s.c.) stimulates locomotor activity in rats, and this effect sensitizes with repeated intermittent treatment. We examined the ability of the AMPA antagonist LY293558, administered systemically over a range of doses (0.1-3.0 mg/kg), to alter morphine sensitization. Pretreatment with 3.0 mg/kg LY293558 attenuated the acute (session 1) locomotor-stimulating actions of morphine, whereas 1.0, 0.3, and 0.1 mg/kg were without effect. No sensitization was observed after repeated morphine treatment (3.0 mg/kg, s.c., every other day for 9 days) when morphine injections were preceded by 0.3, 1.0, or 3.0 mg/kg LY293558, whereas significant sensitization was observed when morphine injections were preceded by vehicle or 0.1 mg/kg of the antagonist. When all rats were challenged with morphine (3.0 mg/kg, s.c.) alone on day 11, the locomotor activity of rats previously exposed to LY293558 at 3.0, 1.0, or 0.3 mg/kg--but not at 0.1 mg/kg--was significantly lower than that of rats previously given morphine preceded by vehicle. On day 13, pretreatment with 1.0 mg/kg LY293558 failed to alter preestablished morphine sensitization in rats previously pretreated with vehicle. These data indicate that LY293558 blocks the development but not the expression of morphine sensitization, confirming a role for AMPA receptors in the initiation of neurobiological adaptations that occur with chronic morphine treatment.

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