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

Abstract

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.

• Authors: S P Mahadik, S Mukherjee
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 38 Issue 4 Pg. 246-54 (Aug 15 1995) ISSN: 0006-3223 [Print] United States
• PMID: 8547447 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• G(M1) Ganglioside
• Choline O-Acetyltransferase
• Haloperidol

Topics

• Animals
• Antipsychotic Agents (administration & dosage, analysis, pharmacology)
• Cerebral Cortex (chemistry, drug effects, enzymology)
• Choline O-Acetyltransferase (metabolism)
• Corpus Striatum (chemistry, drug effects, enzymology)
• G(M1) Ganglioside (administration & dosage, analysis, pharmacology)
• Haloperidol (administration & dosage, analysis, pharmacology)
• Hippocampus (chemistry, drug effects, enzymology)
• Male
• Rats
• Rats, Sprague-Dawley