Memantine does not substantially affect brain stimulation reward: comparison with MK-801

The non-competitive N-methyl-D-aspartate (NMDA)-receptor antagonist MK-801 (dizocilpine) has been shown to potentiate brain stimulation reward (BSR). Memantine (1-amino-3,5-dimethyladamantane) also binds to the PCP binding si te of the NMDA receptor but with markedly different kinetics and affinity t han MK-801. Here, we examined the effects of memantine on BSR and compared its effects to those of MK-801. MK-801 (0.05 mg/kg-0.4 mg/kg) produced clea r, dose-dependent decreases in threshold frequency, manifest in clear leftw ard shifts of the function relating stimulation frequency to response rate. Memantine (1 mg/kg-17.5 mg/kg) had only small effects on threshold frequen cies and only at high doses, manifest in only small shifts in the frequency -response function. The highest dose of each drug also produced a decrease in maximum response rate. This study shows that memantine failed to substan tially influence BSR at low to intermediate doses, suggesting that this sub stance is Likely to be largely devoid of rewarding effects in a therapeutic dose range. (C) 1999 Elsevier Science B.V. All rights reserved.