A single pretreatment with MK-801 or cocaine enhances their locomotor stimulant effects in rats.
A single dose of MK-801 (1.0 mg/kg, s.c.) induces an enhanced locomotor response to a subsequent lower dose of MK-801 (0.3 mg/kg) administered 4, 7 or 14 days later in young adult rats (>90 days). MK-801 (1.0 mg/kg) administration did not significantly enhance the effects of cocaine (10, 20 mg/kg) administered 7 days later. Cocaine (20 mg/kg) enhanced the effect of a subsequent dose of 10 mg/kg cocaine, but did not significantly alter the response to a higher dose cocaine (20 mg/kg) or of MK-801 (0.1 or 0.3 mg/kg) again given 7 days later. MK-801 (1.0 mg/kg) did not significantly enhance the locomotor response to a second dose of MK-801 (0.3 mg/kg) in 28-day-old rats tested 7 days after the initial dose, but did enhance the effects of a lower (0.1 mg/kg) dose. These findings indicate that even a single dose of a stimulant such as MK-801 and cocaine can induce enduring changes in sensitivity to subsequent doses of the same stimulants in young adult rats. The lack of significant effects seen in cross-sensitization studies suggests that separate mechanisms maybe involved in the sensitization to cocaine and MK-801. The more pronounced enhancement of activity in the older animals is in accord with previous findings that sensitization processes are developmentally regulated.
Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, GU20 6PH, UK. oneill_michael_f@lilly.com
M F
MF
O'Neill
G J
GJ
Sanger
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000008:administration & dosage* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D016291:Dizocilpine Maleate; D003042:Cocaine