TY - JOUR
T1 - Responses of dopaminergic and serotonergic systems to triethyllead intoxication
AU - DeHaven-Hudkins, D. L.
AU - Schulz, D. W.
AU - Walsh, T. J.
AU - Mailman, Richard
N1 - Funding Information:
This work was supported by USPHS grants ES-01104 and HD-03110, and training grants ES-07126 and MH-14277. We thank Eddie Stanford, Stan Southerland, Laura Staples and Ronnie McLamb for technical assistance.
PY - 1988
Y1 - 1988
N2 - 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<0.05), with a similar trend in olfactory tubercle and striatum (p<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.
AB - 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<0.05), with a similar trend in olfactory tubercle and striatum (p<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.
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U2 - 10.1016/0892-0362(88)90029-3
DO - 10.1016/0892-0362(88)90029-3
M3 - Article
C2 - 2465482
AN - SCOPUS:0024161204
SN - 0892-0362
VL - 10
SP - 279
EP - 285
JO - Neurobehavioral toxicology
JF - Neurobehavioral toxicology
IS - 4
ER -