Prenatal Ethanol Exposure Impairs Dopamine D\u3csub\u3e2\u3c/sub\u3e and Serotonin Agonist Effects in Rats

Prolonged prenatal exposure to ethanol produces long-lasting alterations in the level of endogenous brain biogenic amines in rats. To test whether there might be long-lived alterations in the reactivity to dopaminergic, serotoninergic or muscarinic agonists in rats exposed prenatally to ethanol, the following study was done. Wistar rats were given 10% (v/v) ethanol in drinking water, starting 10 days before mating and continuing to the end of pregnancy. Male offspring were tested at 3 months for characteristic behavioral effects (oral activity) known to be induced by agonists acting at central dopamine D2 (quinpirole), serotonin 5-HT2C (m-chlorophenylpiperazine, m-CPP) and muscarine (pilocarpine) receptors. Dose-effect curves demonstrated that oral activity responses to quinpirole HCl (0.05-0.40 mg/kg i.p.) and m-CPP 2HCl (0.3-6.0 mg/kg i.p.) were greatly reduced (P \u3c .001) in rats that were exposed to ethanol in utero. Responses to pilocarpine HCl (0.1-3.0 mg/kg) remained unaltered. The findings indicate that prenatal ethanol exposure alters behavioral responses to D2 and 5-HT2C agonists in male rats tested three months after birth. We propose that prenatal ethanol diminishes reactivity of receptors for dopamine D2 and serotonin 5-HT2C receptors

Effect of Pre- and Postnatal Exposure to Zinc on [\u3csup\u3e3\u3c/sup\u3eH] Glucose Uptake in the Brain and Peripheral Tissues of Adult Rats

To determine the susceptibility of developing brain and other tissues to accumulate zinc, rats were exposed to zinc at different periods of ontogeny. For the prenatal group, pregnant Wistar rats received 50 ppm of zinc (ZnSO4 · 7H2O) in drinking for the entire duration of pregnancy. On the day of delivery zinc was removed from the drinking water. Another group, dams, received 50 ppm of zinc in drinking water only during the suckling period (from delivery until the 21st day of postnatal life). Their offspring were weaned on the 21st day, at which time zinc was removed from the drinking water. The control group drank tap water only. At 3 weeks after birth, the level of zinc was estimated in the brain, liver, mandibular bone and kidney of offspring from all groups. At 8 weeks after birth 6-[3H]D-glucose (500 μCi/kg) was administered IP to male offspring, 15 minutes before sacrifice. By liquid scintillation spectroscopy, 3H-activity (expressed as disintegrations per minute [DPM]) was determined in discrete parts of the brain and some peripheral tissues, and expressed as DPM/100 mg of tissue, wet weight. It was found that the highest amount of zinc was accumulated in the brain and liver of rat offspring that were exposed to zinc postnatally. [3H]-activity was at lower levels, in comparison, in nearly all other parts of the brain of rats exposed to zinc postnatally. In offspring receiving zinc prenatally, zinc levels were at similar or lower amounts in the brain and peripheral tissues, vs. the group with postnatal exposure. From this study in rats we conclude that zinc accumulates to the highest extent in brain, following a later ontogenetic (postnatal) exposure period, and by this, there is also greater disturbance of metabolic processes associated with glucose utilization

Effect of Low Frequency Electromagnetic Fields on [\u3csup\u3e3\u3c/sup\u3eH]Glucose Uptake in Rat Tissues

The aims of this study were to evaluate the influence of an extremely low-frequency electromagnetic field (ELF-EMF) on [3H]glucose uptake in the peripheral tissues and organs of rats. Rats were exposed to ELF-EMF (frequency-10 Hz, induction -1.8-3.8 mT) one hour daily for 14 consecutive days. Control animals were sham exposed. On the 15th day (24 hours after last exposure) rats were injected with D-[3H]-6-glucose 500μCi/kg IP. Fifteen minutes later animals were sacrificed by decapitation and peripheral tissues were excised and examined for radioactivity (desintegrations per minute, DPM/ 100 mg wet tissue weight), which expressed [3H]glucose uptake. In most of the examined tissues and organs, such as liver, kidney, heart muscle, cartilage, connective tissue, tendon and skin, [3H]glucose uptake in ELF-EMF-exposed animals was significantly higher as compared to that in the sham control. Exposure to ELF-EMF did not influence [3H]glucose uptake in the thoracic aorta and the skeletal muscle. It is concluded that ELF-EMF impacts tissue glucose uptake by facilitating glucose transport via cell membranes, dependent and probably also independent of its role in increasing insulin action in insulin-dependent tissues

The Effects of Zinc on the Central Dopaminergic System of Rats Prenatally Exposed to Cadmium

On the morning of the first day of pregnancy, Wistar rats were administered a single IP injection of either zinc sulfate (10.0 mg/kg) or saline. For the remainder of pregnancy, half the rats in each group then consumed filtered tap water while the other half consumed filtered tap water with 50 ppm of cadmium (CdCl2). At eight weeks after birth, the behavioral profile of male offspring was assessed in the following way: Apomorphine (non-selective dopamine receptor agonist), (+)-7-hydroxy-2-(di-n-propylamino) tetralin (7-OH-DPAT) (D3 agonist) and (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393) (D1 agonist) were used to evaluate stereotyped behavior, yawning activity and oral movements - indices for these respective agonists. In addition, two dopamine receptor antagonists, haloperidol (D2 antagonist) and 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapine (SCH 23390) (D1 antagonist) were used to evaluate cataleptogenic activity. Additional behavioral parameters studied were locomotor activity, irritability and reaction to a painful stimulus. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) were quantified in the striatum, hippocampus and in the frontal cortex of the brain by means of HPLC/ED technique. In addition, cadmium levels were analyzed in the brain, liver, kidney and bone of newborn rats. Our results indicate that prenatal exposure of pregnant rats to cadmium produced alterations in the reactivity of central dopamine receptors and modulated the level of dopamine and its metabolites in the offsprings\u27 brains. A single injection of zinc, preceding cadmium consumption, attenuated some of the effects of cadmium on the offsprings\u27 dopaminergic system. Zinc also reduced cadmium deposition in the brain, kidney and bone, but enhanced its accumulation in liver. In summary, zinc may exert some neuroprotective effects against cadmium neurotoxicity

Serotoninergics Attenuate Hyperlocomotor Activity in Rats. Potential New Therapeutic Strategy for Hyperactivity

Hyperactivity is thought to be associated with an alteration of dopamine (DA) neurochemistry in brain. This conventional view became solidified on the basis of observed hyperactivity in DA-lesioned animals and effectiveness of the dopaminomimetics such as amphetamine (AMP) in abating hyperactivity in humans and in animal models of hyperactivity. However, because AMPreleases serotonin (5-HT) as well as DA, we investigated the potential role of 5-HT in an animal model of hyperactivity. We found that a greater intensity of hyperactivity was produced in rats when both DA and 5-HT neurons were damaged at appropriate times in ontogeny. Therefore, previously we proposed this as an animal model of attention deficit hyperactivity disorder (ADHD) - induced by destruction of dopaminergic neurons with 6-hydroxydopamine (6-OHDA (neonatally) and serotoninergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) (in adulthood). In this model effects similar to that of AMP(attenuation of hyperlocomotion) were produced by m-chlorophenylpiperazine (m-CPP) but not by 1-phenylbiguanide (1-PG), respective 5-HT2 and 5-HT3 agonists. The effect of m-CPP was shown to be replicated by desipramine, and was largely attenuated by the 5-HT2 antagonist mianserin. These findings implicate 5-HT neurochemistry as potentially important therapeutic targets for treating human hyperactivity and possibly childhood ADHD