Chronic NMDA receptor blockade in early postnatal period, but not in adulthood, impairs methamphetamine-induced conditioned place preference in rats

• Rats with chronic NMDA receptor blockade were tested in conditioned place preference in adulthood.
• Early postnatal NMDA receptor blockade impaired conditioned place preference induced by methamphetamine.
• The same treatment in adulthood did not produce impairment.
• Abnormal development by NMDA receptor blockade may cause classical conditioning deficit.

Early postnatal glutamatergic N-methyl-d-aspartate (NMDA) receptor blockade in animals is known to produce various behavioral deficits in adulthood. In the present study rats postnatally (day 7–20) treated chronically with MK-801, an NMDA receptor antagonist, were tested later in adulthood in methamphetamine (MAP)-induced conditioned place preference (CPP) using a unbiased procedure in a three-compartment apparatus. Rats with the same chronic treatment in adulthood were also tested. CPP test consisted of a baseline test before conditioning, place conditioning, and a preference test after conditioning. Rats postnatally treated with MK-801 did not show any evidence of preference for MAP-paired compartment compared with that for unpaired one in the preference test that was shown in rats postnatally treated with saline. On the other hand, rats treated with MK-801 in adulthood were not affected by the treatment and showed significant CPP as was shown in saline-treated control animals. Results suggest the possibility that chronic early postnatal, but not adulthood, NMDA receptor blockade induces persistent deficit of subsequent appetitive classical conditioning.