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Psychopharmacological effects of MK-801 in infant and preweanling rat pups
L Rajachandran1, G A Goodwin, L P Spear
1Department of Psychology, State University of New York, Binghamton 13902.
Insights
MK-801 exhibits dose-dependent effects on young rats. Low doses stimulate behavior, while higher doses cause sedation in neonatal and preweanling rat pups.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- MK-801 is an NMDA receptor antagonist.
- Its effects on behavior in adult animals are well-documented.
- Understanding developmental neurotoxicity is crucial.
Purpose of the Study:
- To investigate the behavioral effects of MK-801 in neonatal and preweanling rats.
- To determine dose-dependent responses in young Sprague-Dawley rat pups.
Main Methods:
- Neonatal (3-4 days) and preweanling (17-18 days) Sprague-Dawley rats received subcutaneous MK-801 at doses ranging from 0.01 to 1.0 mg/kg.
- Behavioral assessments included forward locomotion, mouthing, headlift, and sniffing.
Main Results:
- Low doses (0.1 mg/kg) of MK-801 induced behavioral stimulation (e.g., increased locomotion) in both age groups.
- Higher doses (0.5-1.0 mg/kg) resulted in sedative effects (decreased locomotion, headlift, sniffing).
- Stimulatory effects were less pronounced in young rats compared to adults.
Conclusions:
- MK-801 displays biphasic effects in developing rats, with low doses being stimulatory and high doses inhibitory.
- These findings highlight potential developmental neurotoxicity and age-dependent responses to NMDA receptor antagonists.
Abstract:
-Neonatal (3-4-day-old) and preweanling (17-18-day-old) Sprague-Dawley rat pups were tested following SC administration of saline, 0.01, 0.05, 0.1, 0.5, or 1.0 mg/kg MK-801. In neonatal rat pups, reductions in a number of behaviors (forward locomotion, mouthing) were seen at the higher (0.5 and 1 mg/kg) doses. In contrast, evidence of behavioral stimulation in forward locomotion at 30 min postinjection was seen at a lower dose (0.1 mg/kg). In preweanling rat pups, marked sedative effects of MK-801 were seen at higher doses (decreases in forward locomotion, headlift and sniff), with signs of behavioral stimulation (increases in forward locomotion and mouthing) evident at low doses. Thus, as in adults, low doses of MK-801 may be behaviorally stimulatory and higher doses inhibitory to both neonatal and preweanling pups, although the stimulatory effects appear to be somewhat less pronounced in these young animals than has been previously reported in adulthood.