Responses of dopaminergic and serotonergic systems to triethyllead intoxication.
Rats treated with triethyllead (TEL) exhibit a behavioral supersensitivity to challenge with dopamine agonists at 7 days following administration of TEL. In the present series of experiments, some neurochemical mechanisms which may affect this behavioral supersensitivity were detected. Administration of a single dose of TEL chloride (7.88 mg/kg, SC) to male Fischer-344 rats decreased the concentrations of dopamine in hippocampus, and of serotonin in olfactory tubercle, at Day 7 posttreatment. The ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine (one estimate of serotonin turnover) was increased in nucleus accumbens (p less than 0.05), with a similar trend in olfactory tubercle and striatum (p less than 0.10). No changes were detected in binding of [3H]spiperone to D2 dopamine receptors in striatum or olfactory tubercle. However, although basal adenylate cyclase activity was unaltered in TEL-treated rats, the Vmax for dopamine-stimulated adenylate cyclase activity was significantly elevated in olfactory tubercle. Conversely, TEL at micromolar concentrations markedly attenuated both basal and dopamine-stimulated adenylate cyclase activity in vitro in striatal homogenates. These data suggest the hypothesis that administration of TEL to rats results in an up-regulation of D1 dopamine receptors in olfactory tubercle, and that the behavioral supersensitivity of TEL-treated animals to dopamine agonists may, in part, be a result of this receptor supersensitivity.
DeHaven-Hudkins
D L
DL
Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill 27514.
Schulz
D W
DW
Walsh
T J
TJ
Mailman
R B
RB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000633:toxicity*; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013997:Time Factors
D009498:Neurotoxins; D009942:Organometallic Compounds; D011985:Receptors, Serotonin; D012701:Serotonin; D013134:Spiperone; D006897:Hydroxyindoleacetic Acid; C010360:triethyllead; D000242:Cyclic AMP; D004298:Dopamine