Perinatal lead exposure alters locomotion induced by amphetamine analogs in rats.
OBJECTIVE
The precise neurochemical perturbations through which perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy of various psychoactive drugs (e.g., cocaine, opiates) are unknown. The present study considers the role of altered serotonin and dopamine functionality in perinatal lead-psychostimulant interactions.


METHODS
Female rats were administered a 16-mg lead or a control solution (p.o.) for 30days prior to breeding with non-exposed males. Lead exposure was discontinued at weaning (postnatal day [PND] 21). Starting at PND 120, male rats born to control or lead-exposed dams were injected with either PAL-287 or PAL-353, at doses of 0, 2, 4, 8, or 16umol/kg (i.p.) with each dose given prior to an acute (45min) locomotion test. Whereas PAL-287 is a potent releaser of serotonin, PAL-353 is not. Each drug induces comparable release of norepinephrine (NE) and of dopamine (DA).


RESULTS
Control and lead rats exhibited minimal locomotion to PAL-287. PAL-353 produced a dose-dependent activation of locomotion in control rats relative to the effects of PAL-287 in control rats. Lead-exposed rats exhibited a subsensitivity to PAL-353 at doses of 4 and 8umol/kg.


CONCLUSIONS
The subsensitivity of lead rats to PAL-353 is consistent with a lead-induced diminution of dopamine function, an effect noted earlier for the reuptake inhibitor cocaine (Nation et al. 2000). The similar response of lead and control rats to PAL-287 is inconsistent with diminished serotonin function.
Behavioral Neuroscience Program, Department of Psychology, Texas A&M University, College Station, TX 77843-4235, United States.
P Shane
PS
Clifford
Nigel
N
Hart
Richard B
RB
Rothman
Bruce E
BE
Blough
Gerald R
GR
Bratton
Paul J
PJ
Wellman
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D007854:Lead; D012701:Serotonin; D004298:Dopamine
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