Chronic cocaine administration increases tyrosine hydroxylase activity in the ventral tegmental area through glutaminergic- and dopaminergic D2-receptor mechanisms.
Tyrosine hydroxylase activity was measured in the brain of rats treated chronically with saline or cocaine (10 mg/kg, 2 x day, for 7 days). Tyrosine hydroxylase activity was significantly increased in the ventral tegmental area 1, 6 and 12 weeks after the last treatment with cocaine. The increase in tyrosine hydroxylase activity at 6 weeks after the last cocaine injection was prevented by the prior administration of MK-801, haloperidol or clozapine but not by the D1 receptor antagonist, SCH-23390. SCH-23390 produced a significant increase in tyrosine hydroxylase activity when administered with saline. These data indicate that glutaminergic and dopaminergic D2-receptor mediated mechanisms are important in regulating the effect of cocaine on the ventral tegmental area.
National Institute of Mental Health, Neuropsychiatry Branch Neuroscience Center at Saint Elizabeths, Washington, DC, USA. masseraj@dirpc.nimh.nih.gov
J M
JM
Masserano
I
I
Baker
N
N
Natsukari
R J
RJ
Wyatt
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000201:enzymology*
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017470:Receptors, Glutamate; D016291:Dizocilpine Maleate; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D006220:Haloperidol