Biomedical subjects

J R Nation

Publications and source records attributed to J R Nation.

At least 37 records · Page 2Linked to original sources

PubMed1994

Chronic lead exposure attenuates ethanol-induced hypoalgesia.

Adult male rats were exposed to drinking fluid containing either 500 ppm lead acetate (group lead), or an equivalent concentration of sodium acetate (group control) for 61 days prior to pain reactivity testing using a tail-flick procedure. Rats were placed in restraining tubes for a 20 min acclimation period, and then baseline tail-flick latencies in response to a radiant heat source were measured. Subsequently, half the animals from each group were serially injected IP with either 1.0, 2.0, or 3.0 g/kg body weight of a 20% v/v ethanol solution, and the other half were injected with an equivalent volume of saline. Tail-flick latencies were reassessed at 20-min intervals over the next 2 h. Results indicated dose-dependent ethanol-induced hypoalgesia at all doses, but at the two higher doses the magnitude of the hypoalgesic response was significantly greater in the group control animals than in the group lead animals across the 2-h postinjection period. Results are discussed in terms of an attenuation of the pharmacological properties of ethanol by lead.

Analgesics↗

PubMed1994

The effects of cadmium exposure on ethanol pharmacokinetics.

Twenty-four adult male rats were exposed in the home cage to water containing 100 ppm added cadmium chloride. An additional 24 animals were pair-watered with water containing no added cadmium. Following 60 days of exposure to their respective watering regimens, one third of the animals in each exposure group (N = 8/condition) received IP injections of 1.0, 2.0, or 3.0 g/kg ethanol (20% v/v). Serum alcohol concentrations were measured at 15, 30, 60, 120, 180, 240, and 360 min postinjection. Although serum alcohol concentrations increased with dose for both cadmium-exposed and control animals, there was no indication at any dose of group differences. The lack of differences in ethanol pharmacokinetics reported here is instructive with respect to improving our understanding of the mechanisms underlying cadmium/ethanol interactions.

Animals↗

PubMed1994

Attenuation of cocaine-induced elevation of nucleus accumbens dopamine in lead-exposed rats.

Fourteen adult male rats were placed on an ad lib watering regimen where they received water containing 500 ppm lead acetate (group lead) or an equivalent concentration of sodium acetate (group control) for 61 days. Subsequently, a microdialysis cannula was surgically implanted in the nucleus accumbens. Following recovery, the seven animals in group lead and the seven animals in group control were presented with a challenge of 10 mg/kg cocaine HCL (IP). Dopamine efflux was measured prior to and at 20, 40, and 60 min postinjection, using HPLC technology. The results of this experiment showed that cocaine caused a significantly greater increase in extracellular nucleus accumbens dopamine in control animals relative to lead-treated animals.

Animals↗

PubMed1994

Brain stimulation reward following chronic lead exposure in rats.

Adult male rats were exposed to drinking water containing either 500 parts per million (ppm) lead acetate or an equal concentration of sodium acetate for 80 days. Bipolar electrodes were then implanted into the medial forebrain bundle (MFB), and rats were allowed to recover for 7 days. On Day 8 postsurgery, control and lead-treated rats were placed in an operant chamber and shaped to press a lever to receive 200-ms trains of current. Data from a range of current intensities and frequencies were recorded to obtain threshold values for each rat, defined as the stimulation needed to support half-maximal lever responding. Results indicated that chronic lead exposure attenuated the reinforcing effect of brain stimulation. Because of the large number of reward systems mediated by the MFB-nucleus accumbens pathway, these data suggest that a variety of motivational phenomena may be affected by contaminant exposure.

Animals↗

PubMed1993

Chronic exposure to lead attenuates cocaine-induced behavioral activation.

Adult, male rats were exposed to a diet containing 500 ppm (0.05%) lead for 105 days before testing for cocaine-related changes in activity using a Digiscan activity system. Behavioral testing occurred on 6 successive test days. Activity was recorded for 20 min prior to and 40 min after IP injections of either 10, 20, or 40 mg/kg cocaine HCl, with saline injections on the day preceding each drug test day. Cocaine-induced behavioral activation was evident in control diet animals for all three doses (10, 20, and 40 mg/kg). While 10 mg/kg cocaine HCl did not produce behavioral activation in lead-treated animals, both 20 and 40 mg/kg did result in increased activity comparable to that observed in control counterparts.

Animals↗

PubMed1993

The effects of chronic lead exposure on reactivity to frustrative nonreward in rats.

Prior to straight runway training two groups of rats received lead exposure (500 ppm via the drinking water) for 106 days. Two additional groups of animals received access to plain tap water. An 80-trial runway acquisition phase followed an initial 60-day fluid exposure phase. During acquisition one lead-exposed group and one water-exposed group received 50% partial reinforcement training, while the remaining animals received continuous reinforcement training. An 80-trial extinction phase immediately followed acquisition. Acquisition results were characterized by superior performance by the continuous reinforcement animals. The partial reinforcement animals took significantly longer to extinguish the alleyway response than did the continuous reinforcement animals. Moreover, the lead-exposed, partial reinforcement animals took longer to extinguish in the goal section of the runway than did the water-exposed, partial reinforcement animals. Conversely, the lead-exposed, continuously reinforced animals displayed significantly more rapid goal-measure extinction than did the water-exposed, continuously reinforced animals. When interpreted by the classic frustration theory [1,2], these latter two findings are supportive of a heightened emotional reaction being promulgated by lead exposure.

Animals↗

PubMed1993

Chronic cadmium exposure attenuates ethanol-induced hypoalgesia in the adult rat.

Adult male rats were exposed to a diet containing either 100 ppm added cadmium (Cadmium-Diet), or a control diet containing no added chemicals (Control-Diet) for 67 days prior to pain reactivity testing using a tail-flick procedure. Rats were placed in restraining tubes for a 20-min acclimation period, then baseline tail-flick latencies in response to a radiant heat source were measured. Subsequently, half the animals from each group were serially injected intraperitoneally with either 0.5, 1.0, 1.5, or 2.0 g/kg body weight of a 20% v/v ethanol solution, and the other half of the animals were injected with an equivalent volume of saline. Tail-flick latencies were reassessed at 20-min intervals over the next 2 hr. Results indicated dose-dependent ethanol-induced hypoalgesia in the Control-Diet animals for the two highest doses, but ethanol-induced hypoalgesia was evident only at the highest dose for the Cadmium-Diet animals. Further, the magnitude of this hypoalgesic effect was significantly lower for the Cadmium-Diet animals than the Control-Diet animals at the 2.0 g/kg dose. Results are discussed in terms of an attenuation of the pharmacological properties of ethanol by cadmium.

Animals↗

PubMed1991

Effects of cadmium on cocaine-induced changes in activity.

Adult male rats were exposed to a diet that contained 100 parts per million added cadmium or a control diet for 72 days before being tested in a Digiscan activity monitor. During the 1-hr test period, each animal's baseline activity levels were recorded for 20 min. Animals then received intraperitoneal injections of 0, 10, 20, or 40 mg/kg cocaine HCl, and their activity levels were recorded for the remaining 40 min of the test session. The results showed that the 10, 20, and 40 mg/kg doses of cocaine produced behavioral activation in the control-diet animals. For cadmium-treated animals, cocaine-induced behavioral changes at the 10 mg/kg dose were not observed, but increased activity was evident at the two higher doses.

Animals↗

PubMed1991

The effects of dietary lead on ethanol-reinforced responding.

Sixteen adult male rats were presented with a diet containing no added lead (Group Control) or a diet containing 500 ppm inorganic lead (Group Lead) for 60 days. Subsequently, all animals were trained to lever press on an FR 1 reinforcement schedule for an ethanol reinforcer using a food-induction procedure where 20 g of food were presented to deprived animals 1 hr prior to the training session. Gradually, the daily food allotment was shifted to 15 min post-session and the ethanol concentration maintained at 6% (v/v). On a subsequent dose/response test, serial presentations of 1, 2, 4, 8, 16, and 32% ethanol reinforcement (v/v) were presented to both groups of animals. The results from the initial self-administration test using 6% ethanol as the reward outcome showed that Group Lead lever pressed at a significantly lower rate than Group Control. In addition, on the dose/response test control animals increased responding at a lower concentration, and then as dose levels continued to increase, began to decrease responding earlier than lead-treated animals. Apparently, sensitivity to ethanol effects is decreased by lead toxicity. The importance of these data for understanding other metal/alcohol interactions is discussed.

Animals↗

PubMed1991

The effects of cadmium on ethanol self-administration using a sucrose-fading procedure.

Rats were exposed for 70 days to either a diet containing 100 ppm cadmium (Group Cadmium) or a control diet with no additives (Group Control). Subsequently, all animals were trained to lever press for a 20% sucrose solution. Across several phases, sucrose was faded out as the reinforcer and gradually replaced with a 10% ethanol solution. A subsequent operant choice (concurrent) test, during which pressing one lever resulted in a dipper presentation of ethanol and the other lever provided water, was followed by a single-lever test where sucrose was reinstated as the reinforcer. The results showed that although cadmium-treated rats lever pressed more than controls during the early phases of the sucrose-fading procedure, animals exposed to cadmium lever pressed at lower rats than controls for ethanol during the concurrent test. There were no group differences on the final sucrose test. The possibility that cadmium may alter sensitivity to ethanol is discussed.

Animals↗

PubMed1989

Effects of combined lead and cadmium exposure: changes in schedule-controlled responding and in dopamine, serotonin, and their metabolites.

Adult male rats were maintained on 1 of 4 ad-lib diets: Group Control-Diet received a normal laboratory diet that contained no added chemicals: Group Lead-Diet received a diet containing 500 ppm (parts per million) lead: Group Cadmium-Diet received a diet containing 100 ppm cadmium: and Group Lead-Cadmium-Diet received a diet containing both 500 ppm lead and 100 ppm cadmium. After 60 days of exposure to their respective diets, animals were placed on restricted diets (15 g/day) of the identical food received during the exposure period. Each animal was trained to lever press on a fixed-interval 1-min schedule for 21 sessions (1 session day). The results of schedule training showed that lead alone or cadmium alone was associated with increased lever pressing relative to control diet. However, when lead and cadmium were exposed jointly, performance was not significantly different from control performance. Similar attenuation of effects were observed for central neurotransmitter functions. Specifically disturbances in dopamine and serotonin turnover that were produced by lead alone were attenuated by the cotreatment of cadmium and lead. Possible accounts of the apparent antagonism between cadmium and lead are discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Ethanol consumption and free operant avoidance performance following exposure to dietary lead.

Rats were exposed ad libitum to a diet containing either 500 ppm lead (Group Lead-Diet) or a control diet with no added lead (Group Control-Diet). On Day 60 both groups were presented with a 15% ethanol solution (nonchoice test) in the home cage for five days prior to placement on a choice test that presented animals with a 10% ethanol solution and tap water. Concurrently with the choice test in the home cage, animals were placed in operant chambers for one hr (pre-avoidance) prior to a 30 min free operant avoidance session (avoidance) and remained there for one hr (post-avoidance) after training. Throughout avoidance training, the choice test was conducted in the chamber as well as the home cage. In addition to evidence of greater ethanol consumption by Group Lead-Diet rats, the results showed that these animals lever pressed more frequently, but not more efficiently, than Group Control-Diet animals.

Alcohol Drinking↗

PubMed1986

Dietary lead increases ethanol consumption in the rat.

Rats fed either a diet containing 500 ppm (parts per million) Pb (as lead acetate) or an unadulterated control diet for 50 days were offered a 15% ethanol (ETOH) solution in a nonchoice (one-bottle) test situation. The results from this test indicated that Pb-diet animals consumed greater amounts of the ETOH solution than did controls. In a subsequent choice (three-bottle, two-fluid) test situation offering a nonpreferred ETOH solution or tap water as alternatives, Pb-diet animals once again ingested greater amounts of the ETOH solution. These findings are discussed in terms of possible Pb-induced increases in emotionality and the potential stress-reduction properties of ETOH.

Alcohol Drinking↗

PubMed1985

Dietary administration of nickel: effects on behavior and metallothionein levels.

Adult male rats were fed either 0, 10, or 20 mg Ni/kg body weight (as NiCl2) via a 10 g daily food ration. Following 14 days of exposure, animals were trained over a period of 61 days to lever press for food on a VI-2 operant training schedule while continuing to experience the indicated daily doses. Those rats treated with 20 mg/kg Ni lever pressed at a significantly lower rate than controls. Group 10 mg/kg subjects were not significantly different on this behavioral measure than control subjects. Atomic absorption spectrophotometric analysis revealed a dose/response accumulation of Ni in the kidney, but analyses of blood, bone, brain, hair, small intestine, liver, and testes did not show differential agent accumulations. Neither hepatic nor renal metallothionein levels were increased above control levels. These findings were discussed within the framework of other recent behavioral and biochemical studies of heavy metal toxicity.

Animals↗

PubMed1985

The regional distribution of cadmium in the brains of orally exposed adult rats.

Cadmium (Cd) levels were measured in 13 dissected brain regions of adult male rats from 3 treatment groups. Rats (approximately 200 g each) were each fed 10 g/day of diets containing either 20 or 100 micrograms/g (ppm) Cd or control diet to which no Cd was added but contained approximately 0.35 ppm Cd. After 67 days of treatment, the brain of each rat was removed and each was dissected into 13 anatomical regions including olfactory bulbs, frontal cortex, rest of cortex, corpus callosum, hippocampus, amygdalae, corpus striatum, colliculum, tegmentum, thalamus, hypothalamus, pons-medulla, and cerebellum. Cd residues (dry weight) in each sample were determined by flameless atomic absorption spectrophotometry. With exception of the thalamus and olfactory bulbs, each of the brain regions of the 100 ppm Cd rats had more Cd than did those from either the 20 ppm Cd rats or controls which did not differ. There was evidence of selective accumulation of Cd within the olfactory bulbs of control and treated animals. This selective accumulation may be related to anosmia reported in workers with industrial exposure to Cd.

Animals↗

PubMed1984

The effects of oral cadmium exposure on passive avoidance performance in the adult rat.

Step-down passive avoidance acquisition and 24 h retention performance were examined in adult rats given daily doses of either 0, 1, or 5 mg/kg cadmium (Cd) (as CdCl2) via the diet. Results indicated that subjects exposed to the 5 mg/kg Cd diet were less likely to step off a safe platform onto an electrified grid floor than controls. The 1 mg/kg subjects did not differ from controls on this acquisition task. None of the groups showed differential performances on a retention test administered 24 h after acquisition training. These results are discussed in terms of recent claims that Cd exposure enhances emotional reactivity in animals.

Administration, Oral↗

PubMed1984

Effects of acute trimethyltin exposure on appetitive acquisition and extinction performance in the adult rat.

Adult male rats were given one intragastric infusion of either 7 mg/kg trimethyltin chloride (dose calculated as the base of trimethyltin [TMT]) or physiological saline. Twenty-one days after dosing, subjects from each condition were divided into two equal-sized groups and trained with either partial (PRF) or continuous (CRF) reinforcement in a straight alley maze. The acquisition phase of training, lasting 40 trials (4 trials/day), was followed by 20 trials of extinction training (4 trials/day). Analyses performed on total speed revealed that TMT-treated subjects performed at lower levels during acquisition than controls regardless of schedule condition. Also, the rate of resistance to extinction was significantly reduced for treated subjects compared with that of controls regardless of the training schedules used during acquisition. A partial reinforcement extinction effect was observed for both control and TMT-treated subjects, that is, independent of dose regimen; PRF training occasioned greater persistence during extinction than did CRF training. These findings are discussed in terms of their implications for contemporary empirical and theoretical issues relating to TMT-induced hippocampal lesions.

Animals↗

PubMed1984

Conditioned taste aversion in the adult rat induced by dietary ingestion of cadmium or cobalt.

The potential aversive qualities of dietary cadmium chloride (10, 100 mg/kg) or cobalt chloride (20, 100, 200 mg/kg) were evaluated in a conditioned saccharin aversion task. Male Long-Evans hooded rats (n = 42) were trained to drink tap water and ingest 10 grams of chow during daily 60 minute access tests. During the aversion-acquisition phase, a second bottle containing 0.1% sodium saccharin was introduced and the various metal-adulterated diets (10 grams, dose calculated as mg metal base/kg body weight) offered in place of plain chow. During extinction testing, all rats were fed the plain chow. Diets adulterated with cadmium (10 or 100 mg/kg) or cobalt (100, 200 mg/kg) induced marked conditioned saccharin aversions after 2-3 days of exposure and were found to be profoundly resistant to extinction. Both cadmium (100 mg/kg) and cobalt (100, 200 mg/kg) induced a corresponding suppression of intake of adulterated food and significant weight losses. The relation of these aversive effects to the influence of cadmium and cobalt on operant responding for food reward is discussed.

Animals↗