Previous investigations have shown that recurrent exposure to dietary lead or cadmium results in increased volitional intake of ethanol. The present proposal will help define a suitable rationale for interpreting metal/ethanol interactions. Specifically, it is proposed that metal-treated animals may consume more ethanol because the pharmacologic and behavioral effects associated with the drug are attenuated by toxic exposure. In this context, increased consumption by treated animals would be viewed as compensatory. To test this idea, the impact of lead or cadmium toxicity on ethanol-induced changes in motor performance, operant responding, and thermoregulation will be studied. Experiment 1 will expose adult rats to a diet containing 500 ppm lead (as lead acetate) for 60 days prior to testing for ethanol-induced impairment of locomotor activity, roto-rod performance, and the aerial righting reflex. Experiment 2 will 'involve the same behavioral tests, but animals will be exposed to food containing 100 ppm cadmium (as cadmium chloride). Experiments 3 and 4 will examine the effects of metal exposure on the rate-depressant action of ethanol in an operant context (FR 32 water-reinforced responding). Experiments 5 and 6 will test for possible attenuation of ethanol-produced poikilothermia in lead-exposed and cadmium-exposed rats. Experiment 7 will examine the effect of lead and cadmium exposure on ethanol metabolism. In all experiments, a full range of ethanol doses will be used for testing.
| Nation, J R; Burkey, R T; Grover, C A et al. (1994) The effects of cadmium exposure on ethanol pharmacokinetics. Pharmacol Biochem Behav 48:543-6 |
| Burkey, R T; Nation, J R; Bratton, G R (1994) Chronic lead exposure attenuates ethanol-induced hypoalgesia. Pharmacol Biochem Behav 47:227-31 |
| Grover, C A; Nation, J R; Burkey, R T et al. (1993) Lead/ethanol interactions. I: rate-depressant effects. Alcohol 10:355-61 |
| Burkey, R T; Nation, J R; Grover, C A et al. (1993) Chronic cadmium exposure attenuates ethanol-induced hypoalgesia in the adult rat. Alcohol Clin Exp Res 17:423-7 |
| Nation, J R; Burkey, R T; Grover, C A (1993) Lead/ethanol interactions. II: pharmacokinetics. Alcohol 10:363-7 |
