Tm. Tzschentke et Wj. Schmidt, Memantine does not substantially affect brain stimulation reward: comparison with MK-801, BRAIN RES, 845(2), 1999, pp. 192-198
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.