The NMDA antagonist dizocilpine (MK801) attenuates motivational as well as somatic aspects of naloxone precipitated opioid withdrawal.
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine has recently been reported to antagonize certain overt withdrawal signs in morphine dependent rats. The purpose of the present study was to reassess this response and examine the effect of this drug in a model presumably reflective of the motivational impact of withdrawal using the place conditioning technique. Rats were made opiate dependent by the subcutaneous implantation of a 75 mg morphine pellet. Three-4 days later withdrawal was precipitated by naloxone 0.5 mg/kg. Dizocilpine (0.1-0.5 mg/kg) attenuated many of the subsequent behaviours elicited by naloxone, notably diarrhoea, mouth movements, paw shakes and ptosis. In a separate group of morphine dependent rats, naloxone (0.05 mg/kg) precipitated withdrawal produced a clear place aversion. This place aversion was blocked by dizocilpine (0.02-0.1 mg/kg) pre-treatment prior to conditioning. Therefore dizocilpine may modify both motivational and somatic aspects of opioid withdrawal.
Higgins
G A
GA
Clinical Research and Treatment Institute, Addiction Research Foundation, Canada, Toronto, Ontario.
Nguyen
P
P
Sellers
E M
EM
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008297:Male; D009042:Motivation; D009270:Naloxone / Q000627:therapeutic use*; D009294:Narcotics / Q000009:adverse effects*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D016291:Dizocilpine Maleate