| 15265637 |
Mastropaolo J, Rosse RB, Deutsch SI: Anabasine, a selective nicotinic acetylcholine receptor agonist, antagonizes MK-801-elicited mouse popping behavior, an animal model of schizophrenia. Behav Brain Res. 2004 Aug 31;153(2):419-22.
The expression of the alpha7-nicotinic acetylcholine receptor is diminished in selected brain areas of patients with schizophrenia. This diminished expression may account for the pathophysiological deficits of sensory inhibition and smooth pursuit eye movement performance in these patients. Furthermore, the deficits in sensory inhibition and smooth pursuit eye movement performance in schizophrenia appear to be inherited in an autosomal dominant fashion; thus, the "alpha7-nicotinic acetylcholine receptor-deficiency" may be a necessary condition for expression of schizophrenia. This deficit has encouraged speculation about the possible therapeutic benefit of selective alpha7-nicotinic acetylcholine receptor agonist interventions in this disorder. In view of this, we sought to examine the effect of anabasine, a selective alpha7-nicotinic acetylcholine receptor agonist, on popping behavior in mice elicited by MK-801. MK-801, a high affinity analogue of phencyclidine (PCP), is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that binds to the hydrophobic domain of this ligand-gated channel. PCP is known to precipitate a schizophreniform psychosis in susceptible individuals, causing productive (e.g. hallucinations) deficit (e.g. affective blunting, amotivation, and social withdrawal), cognitive and motor symptoms similar to those seen in naturally-occurring schizophrenia. Behaviors elicited by MK-801 in mice reflect a pharmacologically-induced state of NMDA receptor hypofunction (NRH), which has been proposed to exist in schizophrenia. Compounds that attenuate MK-801-elicited behaviors, which are identified in this animal model, may have the potential to treat schizophrenia, including deficit and cognitive symptoms. In the current study, anabasine attenuated MK-801-elicited popping at a dose that did not cause clonic seizures. The development of alpha7-nicotinic acetylcholine receptor agonist interventions for schizophrenia must consider their potential liability to elicit seizure activity. |
66(0,2,2,6) |