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.
Masserano
J M
JM
National Institute of Mental Health, Neuropsychiatry Branch Neuroscience Center at Saint Elizabeths, Washington, DC, USA. masseraj@dirpc.nimh.nih.gov
Baker
I
I
Natsukari
N
N
Wyatt
R J
RJ
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