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J L van de Kamp

Publications and source records attributed to J L van de Kamp.

8 recordsLinked to original sources
PubMed1996

Chronic nicotine and mecamylamine treatment increase brain nicotinic receptor binding without changing alpha 4 or beta 2 mRNA levels.

It has recently been shown using regionally dissected tissue that both chronic mecamylamine treatment and chronic nicotine treatment increase the number of [3H]-nicotine binding sites in mouse brain, and that additive increases in the number of binding sites is observed after cotreatment with the two drugs. The studies reported here extend these findings by using quantitative autoradiographic methods to analyze the brains of chronically treated mice at a finer anatomical level of resolution. DBA/2 mice were chronically infused (i.v.) with saline, 4.0 mg/ kg/hr nicotine, 4.0 mg/kg/hr mecamylamine or both drugs for 7 days. The brains of these mice were subsequently analyzed to determine the effects of chronic drug treatment on [3H]-nicotine binding and on the levels of mRNA encoding the nicotinic receptor subunits, alpha 4 and beta 2. [3H]-Nicotine binding was increased in 37 of 46 brain regions after chronic nicotine treatment (average increase = 66.5%), in 41 of 46 regions after chronic mecamylamine treatment (average increase = 56.5%), and in 45 of 46 brain regions after chronic treatment with both drugs (average increase = 107.1%). The changes in [3H]-nicotine binding produced by the two drugs across brain regions were highly (r = 0.98) and significantly correlated. These results are consistent with the proposal that the same receptors are affected by agonist or antagonist treatment. Chronic treatment had no significant effect on the levels of alpha 4 or beta 2 mRNA as measured by in situ hybridization. Therefore, the increases in [3H]-nicotine binding do not arise from changes in the steady-state levels of either alpha 4 or beta 2 mRNA which are believed to encode the subunits of this nicotinic receptor subtype.

Animals↗
PubMed1995

Response of kynurenine pathway enzymes to pregnancy and dietary level of vitamin B-6.

The kynurenine pathway of tryptophan metabolism produces several neuroactive metabolites including 3-hydroxykynurenine, kynurenic acid, and quinolinic acid. This pathway is sensitive to reductions in vitamin B-6 availability because two key enzymes, kynurenine aminotransferase (KAT) and kynureninase (KYNase), require pyridoxal 5'-phosphate. During pregnancy abnormal concentrations of kynurenine metabolites are also found. We measured the effects of pregnancy and vitamin B-6 availability on KAT and KYNase in liver. DBA/2Ibg and A/Ibg mice were fed diets containing 0.25, 0.5, 2.0, 3.6, or 7.0 mg/kg pyridoxine-HCl (PN-HCl) for 4 weeks. Mitochondrial KAT and cytosolic KYNase were measured in control mice and pregnant mice on gestational days 16-18. The response of the two inbred strains was similar throughout. There were no marked alterations in KAT activity as a function of diet or pregnancy. In contrast, KYNase activities were significantly reduced by dietary restriction of vitamin B-6, and pregnant mice had significantly lower activity than nonpregnant controls for all but the highest dietary level of PN-HCl. These data show that pregnancy has a more pronounced effect on KYNase activity than vitamin B-6 restriction, and that the effects of pregnancy and diet are additive. The alteration in the kynurenine pathway in pregnancy is due to a reduction in KYNase activity, which is resistant to alleviation by vitamin B-6 supplementation.

Animals↗
PubMed1994

Prenatal nicotine alters nicotinic receptor development in the mouse brain.

Maternal smoking during pregnancy may affect development of the child, but little is known about potential mechanisms of these effects. Since chronic nicotine treatment alters brain nicotinic receptors in adults and also evokes tolerance which is regulated by genetic factors, pregnant mice of two inbred strains underwent chronic nicotine infusion to determine whether the developmental pattern of mouse brain nicotinic receptors would be altered. C3H/2ibg and C57BL/6ibg mice were infused SC with saline or 2.0 mg/kg/h nicotine during the last half of pregnancy. The developmental profiles of [3H]nicotine and alpha-[125I]bungarotoxin binding in seven brain regions obtained from the offspring were measured. Prenatal nicotine treatment increased levels of [3H]nicotine binding at birth in the C3H hypothalamus, hippocampus, and possibly the cortex, and in the C57BL cortex. At later ages (20-30 days), [3H]nicotine binding was elevated in the C3H hindbrain, hippocampus, striatum, midbrain, and possibly the cortex. The C57BL hindbrain, hippocampus, midbrain, and cortex also showed increased binding at 20-30 days. Little, if any, effect of prenatal nicotine treatment was observed on the development of the alpha-[125I]bungarotoxin binding site. Since upregulated [3H]nicotine binding returns to control levels in adult animals within seven days following termination of chronic nicotine infusion, it is unlikely that simple upregulation is responsible for the changes observed in 20-30-day-old mouse brains.

Age Factors↗
PubMed1987

Alterations in brain catecholamines during pregnancy.

During pregnancy mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The potential role of brain catecholamines in mediating this behavior was examined in the present study. The concentration and turnover of norepinephrine (NE) and dopamine (DA) were measured in hippocampus, striatum, midbrain and cortex in control, pregnant and delivery-day mice. There were no significant changes from control in DA levels during pregnancy and parturition. The turnover of DA was not altered during pregnancy, except for a small increase in turnover rate in the hippocampus. The concentration of NE decreased during pregnancy, and rose at parturition. This effect was most striking in the hippocampus. The turnover of NE was markedly depressed during pregnancy, with the hippocampus again being most affected. These data imply a role for NE, but not DA in the mediation of increased seizure susceptibility during pregnancy.

Animals↗
PubMed1986

The effect of naloxone administration on pregnancy-associated seizures.

Pregnant mice are more susceptible to flurothyl-induced seizures than are non-pregnant controls. The possibility that the well-known increase in beta-endorphin concentration which accompanies pregnancy was involved in this effect was examined by testing whether naloxone administration could block the increased seizure susceptibility. Pregnant female, control female and male C3H mice were treated with 5-50 mg/kg naloxone 5 min before flurothyl seizure testing. Naloxone markedly increased clonic seizure susceptibility in all three groups at a dose of 50 mg/kg, but had little effect at lower doses. In contrast, naloxone had differential effects on myoclonic seizures in pregnant and control female mice, being anticonvulsant in the controls, but proconvulsant in the pregnant mice. A role for endogenous opiates is unlikely in mediating clonic seizures in pregnant mice, but may be involved in myoclonic seizures.

Animals↗
PubMedDate not supplied

Sensitivity of inbred and selectively bred mice to ethanol.

The Long-Sleep (LS) and Short-Sleep (SS) mice were bred for differences in sensitivity to ethanol as measured by duration of loss of the righting response (sleep time). The foundation population was a heterogeneous stock (HS) which was derived from a cross of eight inbred strains. Ethanol-induced sleep time and waking blood and brain ethanol levels were measured in the eight inbred strains, LS, SS and HS mice. The C3H and ISBI strains were quite resistant to ethanol as measured by sleep time, and only one, RIII, was very sensitive. Waking ethanol concentrations were similar for all of the inbreds, implying a narrow range of central nervous system sensitivity to ethanol. The HS mice had relatively short sleep times and blood ethanol levels equal to most of the inbred. The LS mice were significantly more, and the SS mice significantly less sensitive to ethanol than any of the inbreds or HS mice. These studies suggest that the extremes of CNS sensitivities to ethanol manifested by the LS and SS mice cannot be traced to any of the inbred strains, and must have arisen through the selection process by changes in allelic frequencies of those genes conferring ethanol sensitivity and resistance.

Animals↗
PubMedDate not supplied

Developmental profile of hepatic alcohol and aldehyde dehydrogenase activities in long-sleep and short-sleep mice.

Ethanol is metabolized primarily in the liver by a cytosolic alcohol dehydrogenase (ADH). The product, acetaldehyde, is metabolized to acetate by nonspecific aldehyde dehydrogenases (AHD). Mouse liver contains five major constitutive AHD isoenzymes: mitochondrial high Km (AHD-1), mitochondrial low Km (AHD-5), cytosolic high Km (AHD-7), cytosolic low Km (AHD-2) and microsomal high Km (AHD-3). The Long-Sleep (LS) and Short-Sleep (SS) mice differ in their sleep time response to ethanol as early as 10 days of age, and this difference increases with increasing age. Age- and genotype-related differences in metabolism could account for the pattern of responses seen in these mice. We measured the activity of hepatic ADH and the five AHD isoenzymes in LS and SS mice from 3 days of age to adulthood to determine if there were differences in the developmental profiles of these enzyme activities. We found no sex differences in the developmental profile of either ADH or AHD, and the LS and SS mice have nearly identical ADH and AHD activities with the possible exception of the high Km mitochondrial enzyme activity between days 3 and 6, and the low Km mitochondrial enzyme between days 28 and 32. Thus, it appears that differences in ethanol or acetaldehyde metabolism do not contribute significantly to the differential sensitivity to ethanol between young LS and SS mice or to the differential sensitivity between young and adult mice.

Aging↗