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 site of the NMDA receptor but with markedly different kinetics and affinity than 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 clear, dose-dependent decreases in threshold frequency, manifest in clear leftward shifts of the function relating stimulation frequency to response rate. Memantine (1 mg/kg-17.5 mg/kg) had only small effects on threshold frequencies 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 substantially influence BSR at low to intermediate doses, suggesting that this substance is likely to be largely devoid of rewarding effects in a therapeutic dose range.
Tzschentke
T M
TM
Department of Neuropharmacology, Zoological Institute, University of Tübingen, Mohlstr. 54/1, 72074, Tübingen, Germany. rincewind8@hotmail.com
Schmidt
W J
WJ
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007026:Hypothalamic Area, Lateral / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D008559:Memantine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*
D015259:Dopamine Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008559:Memantine