Comparative studies of intracerebroventricularly administered cysteamine and pantethine in different behavioral tests and on brain catecholamines in rats.
In a passive avoidance test, intracerebroventricular administration (post-trial treatment) of the somatostatin-depleting compound cysteamine decreased the avoidance latency of the rats in a dose-related manner, while the effect of pantethine (which is metabolized to cysteamine) was less pronounced. In open-field studies, both compounds decreased the motor activity (ambulation, rearing) of the animals 15 min after the injection followed by a subsequent recuperation of the locomotor depression. Following pantethine, the ambulation increased during the later tests (60 min, 240 min, 24 hr). Cysteamine decreased the noradrenaline and increased the dopamine and dihydroxyphenyl acetic acid content in the hypothalamus, whereas the effects of pantethine were less expressed. Both compounds slightly decreased the striatal noradrenaline and increased the dihydroxyphenyl acetic acid levels at 15 and 60 min after administration. However, contrary to pantethine, 4 hr after treatment with cysteamine, there was a decrease in dihydroxyphenyl acetic acid concentration in this brain region. These findings suggest that both pantethine and cysteamine attenuate passive avoidance latency after intracerebroventricular treatment. The different efficiency of pantethine and its metabolite cysteamine might be connected to the low pantetheinase activity of the brain tissue; however, some direct effects of pantethine cannot be excluded. The different effects of the two compounds on the open-field activity are possibly associated with the diverse effects of the compounds on the striatal dopaminergic neurotransmission.
Vécsei
L
L
Department of Psychiatry and Neurochemistry, University of Lund, Sweden.
Alling
C
C
Widerlöv
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003543:Cysteamine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010204:Pantetheine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D010204:Pantetheine; D003543:Cysteamine; C005425:pantethine; D004298:Dopamine; D009638:Norepinephrine