Pharmacological characterizations of memantine-induced disruption of prepulse inhibition of the acoustic startle response in mice: involvement of dopamine D2 and 5-HT2A receptors.
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Nakaya K, Nakagawasai O, Arai Y, Onogi H, Sato A, Niijima F, Tan-No K, Tadano T
Pharmacological characterizations of memantine-induced disruption of prepulse inhibition of the acoustic startle response in mice: involvement of dopamine D2 and 5-HT2A receptors.
Behav Brain Res. 2011 Mar 17;218(1):165-73. doi: 10.1016/j.bbr.2010.11.053. Epub 2010 Dec 3.
- PubMed ID
- 21130810 [ View in PubMed]
- Abstract
It has recently been reported that psychotic symptoms in patients such as those with Parkinson's disease dementia (PDD) and Lewy body dementia (LBD) may worsen following treatment with memantine, a non-competitive NMDA receptor antagonist. Prepulse inhibition (PPI) of the acoustic startle response (ASR) is used as a measure for sensorimotor gating and it has been reported that PPI is disrupted by memantine. However, the mechanism of memantine-induced PPI disruption remains unclear. In the present study, we investigated the effects of memantine on PPI of the ASR in mice. Memantine (1.25-20mg/kg, intraperitoneally) increased the ASR and dose-dependently decreased PPI for all prepulse intensities tested. This effect of memantine on PPI was attenuated by pretreatment with the antipsychotics clozapine (3 and 6 mg/kg), risperidone (0.3mg/kg) and haloperidol (0.5mg/kg), the selective D(2) antagonist sulpiride (40 mg/kg) and 5-HT(2A/2C) antagonist ketanserin (2 and 4 mg/kg) but not with the selective D(1) antagonist SCH23390 (0.05 and 0.1mg/kg). Clozapine (6 mg/kg) and risperidone (0.3 mg/kg) significantly attenuated the increased startle amplitude in the memantine-treated groups. These results suggest that involvement of dopaminergic and/or serotonergic neurotransmission may play a crucial role in memantine-induced PPI disruption, and additionally, indicate that blockade of either the D(2) or 5-HT(2A) receptor may prevent disruption of PPI induced by memantine in mice. Conceivably, memantine may exacerbate psychotic symptoms in patients with PDD and LBD.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Memantine Dopamine D2 receptor Protein Humans UnknownAntagonistAgonistDetails