Effects of cysteamine and pantethine on open-field behavior, hypothalamic catecholamine concentrations, and somatostatin-induced barrel rotation in rats.
Cysteamine administered in a dose of 1.95 mM/kg subcutaneously (SC) markedly reduced several open-field behaviors (locomotion, rearing, grooming and defecation), while pantethine, administered in an equimolar dose, reduced the locomotion only. However, administered in a dose of 3.90 mM/kg (SC), pantethine also markedly reduced all open-field parameters. Cysteamine, and to less extent pantethine, reduced noradrenaline, and increased dopamine and DOPAC concentrations in the hypothalamus. It is discussed whether the lower potency of pantethine on open-field behaviors and hypothalamic catecholaminergic neurotransmission is connected with the limited activity of pantetheinase, the cysteamine-generating enzyme. Intracerebroventricularly (ICV) administered somatostatin did not influence the pantethine-induced (1.95 mM/kg SC) behavioral changes in the open-field test. It is possible that the peptide did not reach at the receptor sites in a sufficient concentration because of the reduced endogenous somatostatin content, or that the pantethine-induced noradrenaline depletion is connected with the ineffectiveness of somatostatin. Furthermore, pretreatment with cysteamine (1.95 mM/kg SC) or pantethine (1.95 mM/kg or 3.90 mM/kg SC) attenuated the somatostatin-induced (10 micrograms ICV) barrel rotation, suggesting that the level of endogenous somatostatin may play a role in the pathogenesis of this motor disturbance.
Vécsei
L
L
Department of Psychiatry and Neurochemistry, University of Lund, Sweden.
Alling
C
C
Heilig
M
M
Widerlöv
E
E
D000818:Animals; D003543:Cysteamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010204:Pantetheine / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D010204:Pantetheine; D013004:Somatostatin; D003543:Cysteamine; C005425:pantethine