Haloperidol-induced behavioral supersensitivity is increased by monosialoganglioside treatment in rats without affecting spiroperidol-binding.
In rats, dopamine supersensitivity was induced by haloperidol (HAL) treatment for 3 weeks, either by implanted polymer matrices or by daily i.p. injections (1.0 mg/kg/day). Thereafter, dopamine supersensitivity was tested by measurement of motor activity of the animals after application of the dopamine agonist apomorphine (0.5 mg/kg i.p.) and by determination of the specific D2 dopamine binding sites in the corpus striatum by using [3H]spiroperidol. In both modes of HAL administration, no differences were found in the behavioral and neurochemical parameters. The apomorphine-induced motility was enhanced, and the known up-regulation of the striatal D2 dopamine binding was detected. When monosialoganglioside (GM1) was given daily i.p. for 3 weeks parallel to HAL application, dopamine supersensitivity, as indicated by the apomorphine-induced motility, was enhanced significantly without affecting the striatal D2 dopamine receptor up-regulation. In a subsequent experiment, we reduced the HAL dose and observed the expected D2 dopamine up-regulation. However, GM1 had no effect either on striatal D2 dopamine binding or on motility. A thin-layer chromatography analysis revealed that the endogenous gangliosides pattern in the corpus striatum also remained unchanged after HAL treatment. In conclusion, GM1-induced elevation of behavioral supersensitivity cannot be explained by a direct interaction with the D2 dopamine receptor, but other mechanisms may be involved, such as the modification of second messenger pathways.
Schröder
U
U
Institute of Medical Psychology, Otto v. Guericke University of Magdeburg, Germany.
Schröder
H
H
Augustin
W
W
Sabel
B A
BA
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000032:analysis; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*
D005732:Gangliosides; D017448:Receptors, Dopamine D2; D005677:G(M1) Ganglioside; D013134:Spiperone; D006220:Haloperidol