Effect of cadmium on 24-h variations in hypothalamic dopamine and serotonin metabolism in adult male rats

Abstract

This study was designed to analyze the possible cadmium effects on time-of-day variations of anterior, mediobasal, and posterior hypothalamic contents of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) content in adult male rats. Also DA and 5-HT metabolism, as expressed by the ratio 3,4-dihydroxyphenyl acetic acid (DOPAC) to DA and 5-hydroxyindoleacetic acid (5-HIAA) to 5-HT, respectively, were studied. Adult male rats were given cadmium at a dose of 25 ppm of cadmium chloride in drinking water for 1 month. Age-matched rats having access to cadmium-free water were used as controls. Weight gain for the whole period was not changed by cadmium exposure. The metal accumulated in the hypothalamus of rats. In the three hypothalamic regions, significant 24-h variations of NE and 5-HT concentration were found in controls, while DA content changed rhythmically in mediobasal hypothalamus only. Mean content of NE, 5-HT, and DA of anterior, mediobasal, and posterior hypothalamus decreased after cadmium exposure. After cadmium the 24-h pattern of NE changed only in mediobasal hypothalamus, whereas the metal changed significantly the pattern of 5-HT in all regions. DOPAC to DA and 5-HIAA to 5-HT ratios decreased and were differentially changed in all hypothalamic regions analyzed in cadmium-treated rats. There was a statistically significant relationship between time of administration of metal and time that the change took place in biogenic amines in the hypothalamus. These results indicate that cadmium may depress hypothalamic biogenic amine release.

Effect of cadmium on 24-hour pattern in expression of redox enzyme and clock genes in rat medial basal hypothalamus

“…The results indicate that the inherent transcription, translation, and post-translational modifications that give the clock its own natural rhythmicity (Ramsey et al 2007) is disrupted in rats drinking a low amount of CdCl 2 in tap water. Previous studies form this laboratory indicated that chronic exposure of rats to low doses of Cd affected significantly the circadian variation of pituitary hormone release (Lafuente et al 2003(Lafuente et al , 2004(Lafuente et al , 2005. Presumably, the changes in clock gene expression in MBH, a key region in hormone regulation, play a role in the circadian hormone disruption.…”

“…According to WHO (Wakabayashi et al 1987) one cigarette (containing 0.5-3 lg Cd per gram of tobacco) can result in up to 3 lg daily Cd absorption via the lungs. Chronic exposure to these low doses of Cd causes neuroendocrine and neurobehavioral disturbances in animals and humans (Viaene et al 2000;Lafuente et al 2003Lafuente et al , 2004Lafuente et al , 2005Leret et al 2003).…”

Modulatory Effects of Melatonin on Cadmium-Induced Changes in Biogenic Amines in Rat Hypothalamus

“…/kg(bw)/day, recording that rat water consumption is 20 ml/day. This dose of the metal is approximately 835 times higher than provisional tolerable weekly intake (PTWI) for this metal (World Health Organization 2000), it was employed in previous works of our investigation group (Lafuente et al 2003(Lafuente et al , 2004(Lafuente et al , 2005a, and it is similar to the doses employed by other authors (Cory-Slechta and Weiss 1981; Sugawara et al 1981). Melatonin was dissolved in a small volume of vehicle solution (10% absolute ethanol and diluted in 0.9% NaCl to a dose of 150 mg per 100 g body weight).…”

Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters

“…vehicle injections (0.5 mL/day of sesame oil) during the same period of time to be used as controls. At the end of the treatment, animals were killed by decapitation at 14:00h to avoid the diurnal secretion pattern of biogenic amines and amino acids (2,9). Care was taken to avoid any major stress before sacrifice and the decapitation procedure was completed within 5-10 seconds.…”