Chronic cocaine effects on peripheral biogenic amines: a long-term reduction in peripheral dopamine and phenylethylamine production.
The short- (during 12 h after last treatment) and long- (6 weeks after last treatment) term effects of repeated administration of cocaine on the total output of norepinephrine (NE) and its metabolites (sum NE), dopamine (DA) and its metabolites (sum DA) as well as the excretion of 5-hydroxyindoleacetic acid (5-HIAA) and phenylethylamine were evaluated in rats. The concentration of NE, DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the celiac ganglion after 1, 2 and 3 weeks of repeated cocaine administration were also measured. Sum NE remained unchanged during the cocaine treatment but NE and normetanephrine excretions were significantly decreased and increased respectively. 5-HIAA excretion was significantly reduced only after 3 weeks cocaine treatment. In the celiac ganglion NE and DOPAC contents showed tendencies towards being increased and decreased respectively. DA content was not changed. The excretions of DA, DOPAC, homovanillic acid (HVA) and phenylethylamine were significantly reduced during chronic exposure to cocaine. The above short-term changes in DA and phenylethylamine persisted for periods as long as 6 weeks after 1 week repeated exposure to cocaine. It is concluded that chronic exposure to cocaine can produce preferential long term deficiencies in the production of DA and phenylethylamine in the periphery. Peripheral noradrenergic and serotonergic neuronal systems are apparently minimally affected. The close association between DA or sum DA and phenylethylamine excretion suggest these 2 amines may coexist in the same neuron.
Karoum
F
F
Neuropsychiatry Branch, Saint Elizabeths Hospital, Washington, D.C. 20032.
Fawcett
R W
RW
Wyatt
R J
RJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000652:urine
D001679:Biogenic Amines; D010627:Phenethylamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine