Monosialoganglioside cotreatment prevents haloperidol treatment—associated loss of cholinergic enzymes in rat brain

Effects of monosialoganglioside (GM1 ganglioside) cotreatment with haloperidol (HAL) were studied in rat on the haloperidol treatment—associated changes in cholinergic enzymes, choline acetyltransferase (ChAT), and acetvlcholinesterase (AChE) in three brain regions of interest: striatum, hippocampus, and cerebral cortex. Short-term (8 days) haloperidol treatment significantly increased the levels of both ChAT and AChE in all the three regions of brain, as compared with controls (for ChAT: p < .0001 for all comparisons, and for AChE: striatum: p < .0001; hippocampus: p < .0003; cortex: p < .05). Cotreatment with GM1 ganglioside further increased the ChAT activity relative to haloperidol treatment alone in all three brain regions ( p < .05). The AChE activity was also significantly higher than controls in all three regions ( p < .05 for all comparisons) and higher than haloperidol treatment only in hippocampus ( p < .02). After chronic haloperidol treatment (45 days), ChAT activity in cortex had returned to control values in both HAL and HAL + GM1 groups, with no significant group differences remaining ( p = .10). By contrast, relative to control values, HAL and HAL + GM1 groups both showed lower ChAT activity in the striatum, as well as in the hippocampus ( p < .0001 for both), with significantly lower ChAT activity in the HAL than in the HAL + GM1 group for both areas ( p = < .0001 for both). AChE activity showed a significant difference only between the HAL and HAL + GM1 groups in the cortex ( p = .003), but no significant effects of group were seen on AChE activity in either striatum or hippocampus. These data suggest that the protective effects of GM1 ganglioside cotreatment on haloperidol-induced alterations in cholinergic systems can be relevant for protecting against the complications of neuroleptic-induced parkinsonism.