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.
O'Neill
M F
MF
Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Windlesham, Surrey, GU20 6PH, UK. oneill_michael_f@lilly.com
Sanger
G J
GJ
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