Comparative effects of the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) and 6-hydroxydopamine on hypothalamic noradrenergic, dopaminergic and 5-hydroxytryptaminergic neurons in the male rat.
The intracerebroventricular (i.c.v.) administration of 6-hydroxydopamine (6-OHDA; 50 micrograms X 3) and the systemic administration of DSP4 (50 mg/kg X 2; i.p.), alone and in combination, were compared for their abilities to alter the concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) in selected hypothalamic and extra-hypothalamic (striatum, frontal cortex, hippocampus) regions of the male rat brain. DSP4 markedly lowered NE concentrations in extrahypothalamic regions, and within the hypothalamus produced a mild and variable reduction of NE without altering concentrations of DA, DOPAC or 5-HT. 6-OHDA markedly lowered NE concentrations in all brain regions, but was without effect on DA, DOPAC and 5-HT concentrations in any region analyzed. Combined treatment with DSP4 and 6-OHDA did not produce additional effects on levels of NE, DA and DOPAC over either drug alone, but did cause a mild reduction of 5-HT in several brain regions. These results indicate that systemic treatments with DSP4 per se are not as effective as i.c.v. 6-OHDA in depleting NE in the hypothalamus, and that when the two neurotoxins are administered there appears to be some destruction of 5-HT neurons.
Lookingland
K J
KJ
Chapin
D S
DS
McKay
D W
DW
Moore
K E
KE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis; D006892:Hydroxydopamines / Q000494:pharmacology*; D007031:Hypothalamus / Q000032:analysis*; D008297:Male; D018377:Neurotransmitter Agents / Q000032:analysis*; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D051381:Rats; D012701:Serotonin / Q000032:analysis
D000588:Amines; D001596:Benzylamines; D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D016627:Oxidopamine; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine