Behavioral responses to ethanol in rats perinatally exposed to low lead levels.

Wistar rats were exposed to 220 ppm of lead (Pb) in the drinking water from conception to the end of the nursing period (postnatal day 25). Maternal blood Pb levels at this time were 25 microg/dl. Male offspring were tested at the age of 35 or 70 days. We studied the anxiolytic response to 0.5-2.0 g/kg ethanol in an elevated plus maze test and preference for increasing ethanol solutions (2%, 4%, and 6%, v/v) in a free-choice paradigm; we also determined basal blood levels of corticosterone. Results demonstrated that, at 35 days of age, experimental rats were hypersensitive to the anxiolytic effect of ethanol and showed greater voluntary intake of this drug. In addition, 35-day-old Pb-treated rats exhibited higher basal levels of corticosterone as compared with those of controls. These differences disappeared at 70 days. Our findings are discussed in terms of either Pb-induced alterations in the development of the CNS or higher levels of corticosterone in experimental animals. Possible Pb-ethanol effects interactions are also considered.

[Blood lead levels in children of Cordoba City]. / Niveles de plomo en sangre en niños de la ciudad de Córdoba.

Exposure to environmental lead is a major hazard to public health. International Environmental Agencies have assessed that blood lead concentrations of 10.0-15.0 micrograms/dl or even lower may be a risk factor for children. This survey focussed on environmental lead contamination and tried to provide information about blood lead levels in the children population of Cordoba City. A total of 172 children between 6 months and 9 years of age assisted in health centers and hospitals from December 1995 to December 1996 were surveyed. Lead assessment was performed by atomic absorption spectrophotometry with graphite furnace. Results revealed that 73.3% of the children population studied exhibited blood lead levels lower than 10.0 micrograms/dl; 19.2% evidenced risk concentration levels (10.0-14.9 micrograms/dl) and 7.6% showed concentrations higher than 15.0 micrograms/dl. It was confirmed that children with elevated concentrations lived in areas where numerous car repair shops are located. Three of the subjects lived in slums. From the group with low blood lead levels (< 10.0 micrograms/dl), 25 children lived downtown or near main avenues of heavy traffic and belonged to middle class families. Our survey showed a high occurrence of children with lead levels higher than 15.0 micrograms/dl (7.6%) whose etiology risk factors have been identified. Prevention should be able to cut down this occurrence through a safe control of environmental lead sources.

Niveles de plomo en sangre en niños de la ciudad de Córdoba. / [Blood lead levels in children of Cordoba City]

Exposure to environmental lead is a major hazard to public health. International Environmental Agencies have assessed that blood lead concentrations of 10.0-15.0 micrograms/dl or even lower may be a risk factor for children. This survey focussed on environmental lead contamination and tried to provide information about blood lead levels in the children population of Cordoba City. A total of 172 children between 6 months and 9 years of age assisted in health centers and hospitals from December 1995 to December 1996 were surveyed. Lead assessment was performed by atomic absorption spectrophotometry with graphite furnace. Results revealed that 73.3

of the children population studied exhibited blood lead levels lower than 10.0 micrograms/dl; 19.2

evidenced risk concentration levels (10.0-14.9 micrograms/dl) and 7.6

showed concentrations higher than 15.0 micrograms/dl. It was confirmed that children with elevated concentrations lived in areas where numerous car repair shops are located. Three of the subjects lived in slums. From the group with low blood lead levels (< 10.0 micrograms/dl), 25 children lived downtown or near main avenues of heavy traffic and belonged to middle class families. Our survey showed a high occurrence of children with lead levels higher than 15.0 micrograms/dl (7.6

) whose etiology risk factors have been identified. Prevention should be able to cut down this occurrence through a safe control of environmental lead sources.

Spatial learning in rats exposed to acute ethanol intoxication on gestational day 8.

Pregnant Wistar rats were treated on gestational day 8 (GD 8) with two IP injections of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Offspring were tested in the water-maze task at 45 or 90 days of age. The escape latencies of rats trained with a submerged escape platform at a fixed location were similar between control and experimental rats. Analyses of responses on a probe trial carried out 10 days after the training period, revealed that 90-day-old females prenatally exposed to alcohol were less likely to swim in the target region. No differences were observed in this free-swim trial in 45- and 90-day-old male, and 45-day-old female animals. Binding studies of low-affinity GABAA sites in the hippocampus showed an increase in affinity of [3H]GABAA for their binding sites in 90-day-old female offspring prenatally intoxicated with ethanol. Our results demonstrate that acute intoxication with ethanol on GD 8 did not modify acquisition but impaired the retention of spatial learning only in adult female rats. It is possible that the impaired retention will be consequence of higher GABAA receptor affinity.

Effects of acute ethanol intoxication during pregnancy on central dopaminergic system in male rats.

Pregnant albino rats received 2 IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline, on gestational day (GD) 8. During adulthood, male rats prenatally exposed to alcohol exhibited an increased stereotyped behavioral response to 12 mg/kg of amphetamine (AMPH) or 1 mg/kg of apomorphine (APO), whereas the stereotypy induced by 6 mg/kg of AMPH showed no difference between control and experimental animals. Also, the hypoactivity response elicited by small doses of APO was not significantly affected by the prenatal treatment with alcohol. Analysis of dopaminergic function in the striatum and nucleus accumbens demonstrated no change on dopamine (DA) levels in both structures in alcohol pre-exposed 55- and 180-day-old rats. A reduction in striatum 3-4 dihydroxyphenylacetic acid levels was observed at both ages. These results indicate that an acute intoxication with alcohol on GD 8 induces a long-lasting decrease in striatal but not in nucleus accumbens DA metabolism. As a consequence, a lower striatal DA release might produce a compensatory supersensitivity of postsynaptic DA sites. This interpretation is consistent and correlates with behavioral results.

Acute ethanol intoxication during pregnancy: postnatal effects on the behavioral response to serotonin agents.

Pregnant wistar rats were treated on the eighth day of gestation (GD 8) with two IP injections, spaced by 4 h, of either ethanol (2.9 g/kg in 24% v/v saline solution, EG) or saline (SG). Other pregnant females did not received any type of IP injections (absolute control group, ACG). Offspring were tested at 45 or 90 days of age. At 45 days of age, EG showed an increased behavioral response (forepaw treading and hindlimb abduction) to the 5-HT1 agonist, 5-methoxy-N,N-dymethyltryptamine. In addition, an enhanced "wet-dog" shakes behavioral response to 5-HT2 agonist, 5-hydroxy-L-tryptophan, was also observed in EG as compared to ACG and SG. On the contrary, at 90 days, EG exhibited a diminished behavioral reactivity to 5-HT1 and 5-HT2 agonists as compared to SG. These results demonstrated that acute administration of ethanol on GD 8 induced long-lasting changes in the functioning of central serotonergic systems.

Effect of acute ethanol exposure during pregnancy on dentate gyrus synaptic plasticity in 45-day-old rats.

Pregnant Wistar rats were treated during the eighth day of gestation (GD8) with two IP injections, spaced by an interval of 4 h, of either ethanol (2.9 g/kg in saline solution) or saline. At 45 days of age, rats prenatally exposed to alcohol showed an improved hippocampal synaptic plasticity in granule cells layer of dentate gyrus. This was assessed measuring the threshold to generate long-term potentiation (LTP) on hippocampal slices. We propose that this result might account for the good performance in some learning tasks observed in animals prenatally exposed to alcohol during short periods.

Sexual receptivity of adult female rats prenatally intoxicated with alcohol on gestational day 8.

On gestational day 8 (GD 8), pregnant albino rats received two IP injections, spaced by 4 hours, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Adult females exposed to ethanol in utero showed greater sensitivity to estrogen, but not to estrogen plus progesterone, for induction of lordotic response. The 5-HT1 receptor agonist 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT) had a significantly smaller effect in inhibiting lordosis response in experimental rats. The greater sensitivity to estrogen and lower sensitivity to the receptor agonist could be a consequence of long-term changes in central neurotransmitter systems induced by acute intoxication with ethanol on GD 8.

Acute ethanol exposure during pregnancy in rats: effects upon a multiple learning task.

Pregnant rats received 4.8 g/kg of 20% (v/v) ethanol IP or identical volume of saline during gestational Day 8. No signs of gross physical teratogenesis were evident in the offspring as expressed by litter size, weight and external malformations at birth. However, when offspring were subjected to a multiple fixed ratio-4/differential reinforcement of low rate of responding 10-sec ( FR 4/DRL 10 sec) schedule of reinforcement at 60 days of age, significant differences were observed in the performance of DRL 10-sec schedule that required visual discrimination and response inhibition, but not in the FR 4 schedule that required a relatively simple nondiscrimination task of active-response. Bar press rates were unaffected by prenatal treatment since no differences between groups were found in the number of total responses performed on either component of the multiple schedule. Present results are discussed in terms of either response perseveration or a lower aptitude to deal with low rates of responding-discrimination learning tasks on the animals prenatally exposed to alcohol.

Response to an ethanol challenge dose on sleep time and blood alcohol level in Wistar rats prenatally exposed to ethanol during gestational day 8.

Pregnant albino rats were treated during the eighth day of gestation (GD 8), with two IP injections, spaced by 4 hours, of either ethanol (2.9 g/kg in 24% v/v saline solution) or saline. Maternal blood alcohol levels reached a peak of 457 mg/dl 60 min after the second dose. At the age of 45 days, an equal number of male and female offspring were injected with 3.5 g/kg ethanol and sleep time and blood ethanol levels were determined upon awakening. Ethanol metabolic rate was studied in other individuals injected with the same dose of ethanol and the slope of the linear descending portion of the curves was calculated. Animals that received ethanol in utero exhibited shorter sleep time and higher blood ethanol levels at the moment of awakening than controls. The rate of ethanol metabolism was similar in both groups. These results show that an acute intoxication with ethanol during GD 8 induced long-term changes in the CNS of offspring which caused reduced sensitivity to ethanol hypnotic effects.

Opioid influence on some aspects of stereotyped behavior induced by repeated amphetamine treatment.

Rats were administered repeated IP injections of dl-amphetamine (AMPH) according to a chronic escalating dose schedule (three doses per 24 hr, for four days, two days or one day). Animals treated for four days exhibited a diminished oral stereotypy in response to a challenge of 12 mg/kg AMPH or 2 mg/kg SC apomorphine (APO), 72 hr after withdrawal. Pretreatment with 2 mg/kg IP naloxone (NAL) during the period of chronic AMPH administration prevented the reduction in oral stereotypy induced by AMPH or APO. No differences were detected among the mean of stereotypy scores from the different treatments in response to a challenge dose of 6 mg/kg AMPH. Neurochemical data showed that NAL pretreatment reversed the depletion of striatal dopamine content induced by chronic AMPH. When repeated injections of AMPH were given only one day, the diminished stereotypy response to AMPH or APO was not observed. Animals treated simultaneously with 1 mg/kg IP morphine or 5 micrograms/kg IP beta-endorphin and repeated AMPH injections for one day, showed a reduced stereotyped response to AMPH or APO. These results suggest that opioid peptides are involved in the mechanisms underlying the decrease in oral behaviors following AMPH treatment.

Involvement of a serotonergic control in the regulation of plasma levels of immunoreactive beta-endorphin.

Beta-endorphin immunoreactivity was measured in plasma and hypothalamus of rats treated with alpha-methyl-p-tyrosine (alpha -MT) (two doses of 200 mg/kg) or p-chloro-phenyl-alanine (PCPA) (two doses of 150 mg/kg). It was also measured in plasma after a single dose (5 mg/kg) of amphetamine or after electrical stimulation of median raphe nucleus (MRN). Plasma levels of immunoreactive beta-endorphin (ir B-E) were significantly decreased by PCPA and were elevated by electrical stimulation of MRN. Alpha -MT was ineffective to modify ir B-E plasma concentration as well as amphetamine. These findings suggest a role for 5-hydroxytryptamine (5-HT) in the regulation of plasma B-E content.

Involvement of a serotonergic control in the regulation of plasma levels of immunoreactive beta-endorphin.

Beta-endorphin immunoreactivity was measured in plasma and hypothalamus of rats treated with alpha-methyl-p-tyrosine (alpha -MT) (two doses of 200 mg/kg) or p-chloro-phenyl-alanine (PCPA) (two doses of 150 mg/kg). It was also measured in plasma after a single dose (5 mg/kg) of amphetamine or after electrical stimulation of median raphe nucleus (MRN). Plasma levels of immunoreactive beta-endorphin (ir B-E) were significantly decreased by PCPA and were elevated by electrical stimulation of MRN. Alpha -MT was ineffective to modify ir B-E plasma concentration as well as amphetamine. These findings suggest a role for 5-hydroxytryptamine (5-HT) in the regulation of plasma B-E content.

Effect of naloxone and amphetamine on acquisition and memory consolidation of active avoidance responses in rats.

Pretraining IP injection of naloxone (0.3 mg/kg) or amphetamine (2 mg/kg) enhanced performance during acquisition, but did not improve retention of active avoidance responses in rats. Naloxone (0.1 or 3 mg/kg) had no effect on acquisition or on retention. The combination of naloxone (0.3 mg/kg) plus amphetamine (2 mg/kg) did not produce the facilitation observed when each of the two drugs was administered alone. Pretreatment with the higher dose of naloxone (3 mg/kg) blocked the facilitative effect of amphetamine on acquisition. Post-training administration of naloxone (0.3 mg/kg) or amphetamine (2 mg/kg) improved retention. Naloxone (0.1 or 3 mg/kg) had no effect. When naloxone and amphetamine were combined, at respective doses of 0.3 mg/kg and 2 mg/kg, the improvement did not occur, i.e., the higher dose of naloxone prevented the facilitative effect of amphetamine. In addition, an ineffective dose of amphetamine (0.5 mg/kg), given either pre- or post-training together with the lower dose of naloxone (0.1 mg/kg), produced a significant enhancement of acquisition or consolidation, respectively. The results are consistent with the possibility that naloxone might exert its facilitative action on acquisition and memory consolidation through the release of catecholaminergic systems from inhibitory influences of opioids.

Inhibition of catecholamine biosynthesis and memory processes.

Rats injected with 60 mg/kg of alpha-methyl tyrosine (alpha-MT) immediately after a training in a shuttle box impaired retention of conditioned avoidance response (CAR). DL-Dopa (200 mg/kg) administered 5, 30, 60, and 120 min after alpha-MT treatment counteracted the depressive effect of this drug during the retention test; at longer times it was ineffective. Post-trial injections of 600 mg/kg of diethyldithiocarbamate (DDC) impaired retention of CAR; at a lower dose (300 mg/kg) it had no effect. Administration of alpha-MT (60 mg/kg) immediately after passive avoidance training lowered memory in females but not in males. These results suggest that noradrenaline (NA) is required for memory consolidation processes for about 2 h after training.