Loy D. Lytle

Effects of long-term corn consumption on brain serotonin and the response to electric shock.

Rats fed tryptophan-poor corn diets have reduced levels of brain serotonin and show increased responsiveness to electric shock. This diet-induced hyperalgesia can be reversed by feeding the animals diets with adequate amounts of tryptophan, or by systemic injections of the amino acid.

Interaction of diet and drugs in the regulation of brain 5-hydroxyindoles and the response to painful electric shock

Abstract The long-term consumption of a tryptophan-poor, corn diet by rats decreases electroshock response thresholds. This hyperalgesia appears to be related directly to diet-induced reductions in the brain concentrations of the putative neurotransmitter, serotinin. Rehabilitating corn-fed animals by feeding them the corn diets supplemented with tryptophan restores brain serotonin and pain thresholds to normal; similarly, injecting the tryptophan-deficient, corn-fed animals with fluoxetine, a drug that blocks the uptake of serotonin into brain neurons, also restores the electroshock response thresholds to control levels. The tryptophan hydroxylase inhibitor, p -chlorophenylalanine, increases the hyperalgesia to electroshock in corn-fed rats and further reduces brain serotonin concentrations. Injection of the amino acid valine, on the other hand, produces hyperalgesia and decreases brain serotonin in casein-fed rats but not in animals fed the corn diet. These data lend support to the hypothesis that serotonin neurons may mediate the sensitivity or reactivity to painful stimuli.

Long-term effects of 5,7-dihydroxytryptamine administered at birth on the development of brain monoamines

Summary 5,7-Dihydroxytryptamine (12.5, 25.0, or 50.0 μg) was injected intracisternally in male and female rats at birth; animals were killed 3, 12, 24, or 60 days after the injections and brain monoamines were examined for changes in the concentrations of various neurotransmitters. Brain serotonin levels were markedly depleted at all time periods examined, with the greatest reduction occurring after the injection of 50 μg of the drug. In animals killed at 60 days of age, decreases also occurred in the concentrations of brain and spinal cord 5-hydroxyindoleacetic acid and brain norepinephrine, although the depressions in brain norepinephrine were small (73% of controls) and non-dose related. Spinal cord, and regional and whole brain levels of serotonin and 5-hydroxyindoleacetic acid were still decreased 120 and 240 days after injection. Whereas brain norepinephrine was also depressed at 240 days of age, brain levels of tryptophan or dopamine, and cardiac levels of norepinephrine, were unchanged.

Effects of p-chloroamphetamine on locomotor activity and brain 5-hydroxyindoles

Abstract p-chloroamphetamine increased locomotor activity in rats for up to three days following a single injection; the peak increase in drug-induced activity occurred on the second day. Spinal cord and brain regional concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid were reduced within two days after administration of p-chloroamphetamine, with the greatest reductions occurring in forebrain areas. Brain 5-hydroxyindoles were still reduced in all areas except the midbrain and spinal cord for as long as one week after drug treatment. The effects of p-chloroamphetamine on both locomotor activity and brain 5-hydroxytryptamine were blocked by pretreatment with Lilly 110140, a selective uptake inhibitor in brain serotonin neurones. These results suggest that brain serotonin neurones may normally inhibit locomotor activity and that p-chloroamphetamine destroys this inhibitory system. The basal levels of activity return to normal even though brain serotonin is reduced chronically. The possible reasons for these effects are discussed.

Long-term effects of 5,7-dihydroxytryptamine on brain monoamines

Abstract 5,7-dihydroxytryptamine (75 and 150 μg) was injected intraventricularly to adult male rats; animals were killed at various times after the injection and brains were examined for changes in the concentration of tryptophan, serotonin, 5-hydroxyindole acetic acid, norepinephrine and dopamine. Brain 5-hydroxyindoleamines were markedly depleted at all time periods examined, even after the administration of a tryptophan load (50 mg/kg). A small but significant decline in brain norepinephrine but not dopamine was also noted after the administration of the dihydroxytryptamine.

Effects of lateral hypothalamic lesions on consummatory behavior in developing rats

Bilateral lesions aimed at the lateral hypothalami of preweanling rats result in decreased weight gain and eventual death within 5 days after the operation. Ten-day-old rats with unilateral damage to the lateral hypothalamus show retarded growth, food and water intake regulatory deficits, and altered sensitivity to quinine adulteration of the water for up to 60 days of age. These results suggest that at least one neural mechanism that regulates food and water intake matures early in the postnatal life of the rat.

L-tryptophan and rat fetal brain serotonin

Abstract Rat fetal brain and body tryptophan, and brain serotonin were measured at 15, 17, and 19 days postconception, and on the day of birth. Body tryptophan and brain serotonin increased with age during the last trimester of pregnancy; brain tryptophan increased only slightly during this time period. L-tryptophan injected into the mother or into neonates increased fetal and neonatal body and brain tryptophan, and brain serotonin at all ages studied. The dose- and time-relationships of 1-tryptophan-induced changes in brain tryptophan and serotonin were evaluated in 19 day old fetuses. The systemic administration of 1-tryptophan directly to the 19 day old fetus also increased brain serotonin. Thus, fetal brain serotonin neurons appear to have the capacity to synthesize the neurotransmitter from exogenously administered tryptophan, even though these neurons appear to be relatively immature.

BRAIN AND PERIPHERAL MONOAMINES: POSSIBLE ROLE IN THE ONTOGENESIS OF NORMAL AND DRUG-INDUCED RESPONSES IN THE IMMATURE MAMMAL

The ability of the developing, nonprecocial newborn mammal to produce mature physiological and behavioral responses may in part depend upon the functional status of monoamine-containing neurons in the brain and periphery. Alterations produced in the patterns of locomotor activity, elective food consumption, and thermoregulation produced by various drugs thought to act via monoaminergic neurons, also change as a function of the age of the organism. Monoamine-containing neurons are not fully mature at birth in neonatal animals such as the rat: they are less able to synthesize, store, inactivate, release, and respond to neurotransmitters than are corresponding neurons in adult animals; moreover, not all of their synaptic connections have been made. The significance of changes in the developing monoamine neurons are discussed in relationship to their roles in determining the course of physiological and behavioral ontogenesis.

Maternal meal quality alters fetal rat brain serotonin concentrations

Abstract The quality of food eaten by pregnant animals may influence fetal neurotransmitter biosynthesis by altering the relative availability of precursor amino acids. Fetal brain concentrations of tryptophan and the neurotransmitter serotonin increase following the consumption of a carbohydrate-fat meal or after the injection of insulin in fasting animals; in contrast, the fetal concentrations of these compounds are reduced in animals whose mothers eat a meal containing casein protein or amino acids which compete with tryptophan for uptake from maternal blood into the placenta and fetus.

Blockade of endotoxin-induced hypothermia by pretreatment with intracisternal 6-hydroxydopamine

Abstract Endotoxin-induced hypothermia was blocked in rats by pretreatment with intracisternally-applied 6-OHDA but not by systematic pretreatment with 6-OHDA or by pretreatment with the dopamine receptor blocking agent, pimozide. These data suggest that brain norepinephrine-containing neurons may in part mediate the thermic changes that result from challenge with endotoxin.