Rationale: Psychotomimetic N-methyl-D-aspartate/glutamate receptor antagonists, such as phencyclidine (PCP), have been shown to produce a spectrum of behavioral, neurochemical and anatomical changes in rats that are relevant to aspects of schizophrenia, including impairments of working memory and visual attention. The alpha(2) noradrenergic receptor agonist clonidine prevents some of the behavioral effects of NMDA antagonists, suggesting that monoaminergic systems mediate some aspects of these deficits.
Objectives: We sought to determine the ability of clonidine to modify the PCP-induced deficits of visual attention and spatial working memory in rats.
Results: In a lateralized reaction time task, a lower dose of clonidine (10 microg/kg) ameliorated the impairment of choice accuracy produced by PCP (2.5 mg/kg, IP), while the higher dose of clonidine (50 microg/kg) slowed response times and induced a deficit of choice accuracy on its own. The high dose of clonidine effectively prevented the motor impulsivity produced by PCP. In addition, clonidine (10 microg/kg) prevented PCP-induced performance deficits in a delayed non-match to sample task.
Conclusions: These data indicate that clonidine may attenuate deficits of attention and working memory produced by PCP, perhaps in part by preventing some of the downstream neurochemical and anatomical effects of this psychotomimetic drug.