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 acetylcholinesterase (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 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.
Department of Psychiatry and Health Behavior, Medical College of Georgia and Research Service, Veterans Affairs Medical Center, Augusta 30910, USA.
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Mahadik
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Mukherjee
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D006220:Haloperidol / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase; D006220:Haloperidol