Maturational changes in the thermal nociceptive responses of developing rats.

Some find developmental differences in rodent thermal nociceptive responses and others do not. To address these inconsistencies, the escape latencies of immature (5-to 25-day-old) and adult (3-to 4-month-old) albino rats were recorded following tail exposure to different intensities of radiant heat (650-W halogen lamp placed 10-30 mm from the tail) or conductive heat 35-50 degrees C water). Developmental differences in tail flick latencies were not observed in immature rats when the lamp was closest to the tail (although adult latencies were longer than 5-and 15-day-old responses) When radiant heat intensity was reduced, 5-day-old rats had shorter escape latencies than 15-, 25-, and 90-day-old animals. Age differences persisted in the latencies of immature animals even when the test aperture was varied to compensate for maturational changes in tail width (whereas adult responses no longer differed from those of 5-and 15-day-old rats). Developmental differences were eliminated when the tail skin was blackened so as to normalize the absorption of radiant heat across age. Similar age-and intensity-dependent differences were observed in rats exposed to conductive heat: Five-and 10-day-old pups had shorter escape responses than older rats when tails were immersed in intermediate (40 or 45 degrees C) but not lower (35 degree C) or higher (50 degrees C) temperature water. Blackening the tails did not change conductive heat escape latencies. No sex differences were found at any age or stimulus intensity with either type of heat. Higher intensities of thermal stimuli applied to the tail are required to elicit escape responses in older rats compared to younger ones, but the use of relatively intense thermal test stimuli can mask age-dependent differences in nociception. Some of the inconsistent results reported previously about maturational changes in thermal nociception may be due to intensity differences in the noxious test stimuli used. Maturational differences in the radiant absorption properties of the tail seem to account for most of the age-related changes in rodent responses to radiant heat, but the mechanism(s) which subserve developmental differences in conductive heat nociception need to be elucidated.

Light-induced changes in pineal gland N-acetyltransferase activity: developmental aspects.

In adult rats, light acting via a retino-pineal gland neural pathway influences pineal gland biochemistry in two ways: (1) it entrains endogenous circadian rhythms in melatonin biosynthesis to the environmental photoperiod and (2) exposure to even very brief periods of light during the nighttime rapidly suppresses the high levels of nocturnal melatonin production. The present studies were undertaken to determine precisely when photic stimulation first influences the enzymic activity of N-acetyltransferase (NAT), the pineal gland enzyme which rate-limits the overall biosynthesis of the hormone melatonin, and to examine some of the cellular mechanisms which might mediate light-induced effects in neonatal animals. Rats of different ages were either killed during the light phase or were exposed to darkness or light for 1 min during the dark phase of the lighting cycle, returned to their litters in darkness for 30 min and then killed. Pineal gland NAT activity in animals nocturnally exposed to 1 min of light was suppressed in animals 6 days of age or older. Nocturnal light exposure did not suppress enzyme activity in 3- to 5-day-old rats, even though these animals displayed clear light:dark differences in pineal gland NAT activity. Nocturnal light exposure also did not suppress nighttime levels of NAT activity in 7-day-old animals who had been bilaterally enucleated, suggesting that this effect is retinally mediated. Pretreatment of 7-day-old animals with the beta-noradrenoceptor agonist drug, isoproterenol, prevented the nocturnal light-induced suppression of NAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Light affects neonatal rat pineal gland N-acetyltransferase activity by an extra-retinal mechanism.

To determine whether extra-retinal mechanisms mediate photoperiodic changes in neonatal rat pineal gland N-acetyltransferase activity, 4-day-old intact or bilateral orbital enucleated rats were killed during the dark phase of the lighting cycle, either in darkness or following 4 hr exposure to fluorescent light. Light suppressed the high nighttime N-acetyltransferase activity equally in intact and enucleated pups. Subsequent studies showed that at least 0.5 hr exposure and nocturnal illuminances of 109 microW/cm2 or greater were required to cause statistically significant reductions in the activity of the enzyme in 4-day-old rats. Taken together, these data indicate that relatively intense environmental light can affect neonatal rat pineal gland biochemistry via extraretinal mechanisms.

Xylamine enhances pineal gland N-acetyltransferase activity in vitro.

1. The action of N-2'-chloroethyl-N-ethyl-2-methyl benzylamine (xylamine) on rat pineal gland sympathetic innervation was examined. 2. This alkylating agent caused a concentration-dependent increase in pineal gland N-acetyltransferase (NAT) activity in neurologically intact pineal glands that was suppressed in glands previously subjected to bilateral superior cervical ganglionectomy. 3. Xylamine-induced elevations in NAT activity were attenuated by beta-noradrenergic antagonist drugs but not by alpha-noradrenergic antagonist drugs. 4. Since pineal gland uptake of radiolabelled norepinephrine (NE) was impaired by xylamine, the drug may increase pineal gland NAT activity by inhibiting NE reuptake into the presynaptic nerve terminal, thereby increasing the amount of the neurotransmitter available to stimulate pinealocyte beta-noradrenoceptors.

Catecholaminergic mechanisms mediate hypothermia-induced elevations in pineal gland N-acetyltransferase in neonatal rats.

The newly born of many mammalian species are ectothermic, and it is possible that biochemical processes important for the metabolism of endocrine hormones might vary with alterations in the environmental temperature. Temperature-induced fluctuations in pineal gland N-acetyltransferase activity were investigated in 4-, 12-, and 20-day-old rats placed for 4 hr in 23 or 34 degrees C environments. Enzyme activity increased dramatically in ectothermic 4- and 12-day-old animals exposed to the 23 degrees C environment, but not in endothermic 20-day-old rats. The elevations in daytime pineal gland NAT activity seen in cold-exposed animals were absent in rats previously subjected to chemical sympathectomy induced by 6-hydroxydopamine, or in animals treated with the beta-noradrenoceptor antagonist drug propranolol. Catecholaminergic nerves and beta-noradrenoceptors known to be important for light-induced changes in mammalian pineal gland biochemistry also appear essential for environmental temperature-dependent elevations in neonatal pineal N-acetyltransferase activity.

Extraretinal mechanisms mediate light-induced changes in neonatal rat pineal gland N-acetyltransferase activity.

Nocturnal light-induced changes in pineal gland N-acetyltransferase activity were investigated in intact or enucleated 4-, 6-, or 8-day-old maternally isolated rats maintained at different ambient temperatures. Nighttime enzyme activity was increased markedly in rats maintained in 23 degrees C compared to 35 degrees C environments. Four hours of nocturnal light significantly reduced N-acetyltransferase activity in intact rats at all ages studied when the animals were maintained at 35 degrees C. Shorter duration (1 min) nocturnal light reduced N-acetyltransferase activity in intact rats 6 days of age. However, the enzyme activity suppression observed after the 4 hr of nocturnal light was still present in 4-day-old rats (but not older animals) even when the younger animals had been made blind by bilateral orbital enucleation. Taken together, these data suggest that an extraretinal mechanism may mediate light-induced changes in some aspects of pineal gland indoleamine biochemistry in newborn rats.

Action spectrum of the retinal mechanism mediating nocturnal light-induced suppression of rat pineal gland N-acetyltransferase.

The spectral properties of the retinal mechanism mediating the inhibitory effects of nocturnal light on pineal gland N-acetyltransferase (NAT) activity were determined. Pineal gland NAT activity declined linearly in albino rats exposed to different irradiances of a 460 or 580 nm monochromatic light during the middle of the dark phase of the cycle. The difference in sensitivity to the test lights is that predicted for a photopigment having peak absorbance at 495 nm, suggesting the inhibition of pineal gland N-acetyltransferase activity is mediated by the photopigment found in rat rods.

Inhibition of rat brain and liver protein synthesis by amphetamine.

Dose-dependent, amphetamine-induced reductions in protein synthesis were determined in vivo by measuring [3H]lysine incorporation into trichloroacetic acid precipitated protein in homogenates prepared from different regions of the brain or liver. Low-to-moderate doses of amphetamine (1-5 mg/kg) decreased striatal protein synthesis whereas higher doses (10 mg/kg) reduced it in the cerebral cortices, cerebellum, and remaining portions of the cerebrum, as well as in the striatum and liver. Reductions in regional brain protein synthesis occur following amphetamine treatment in relatively low doses known to change various aspects of physiology and behavior.

Visceral nociception in developing rats.

Maturational changes in visceral nociception were measured in developing or adult rats challenged with hypertonic saline or acetylcholine. Chemically induced abdominal constrictions were absent in rats younger than 7 days of age, regardless of the dose of hypertonic saline or acetylcholine used. Age-related increases in the percent of animals responding, the number of abdominal constrictions emitted per responder, and total response duration occurred in animals 10-20 days of age, until adult-like patterns of responding were attained at the time of weaning. Additional changes in the percent animals responding, as well as in the frequency and total duration of abdominal constriction responses, were also seen in postweanling, but not in preweanling, animals. Five-day-old animals did emit audible vocalizations to the intraperitoneal insertion of a hypodermic needle, however, at a time when these animals failed to show observable responses to the noxious visceral stimuli. Hence, mechanisms mediating pain associated with intraperitoneal needle insertion may be functional during the first postnatal week, at a time when mechanisms mediating visceral pain appear to be immature. These differences may be caused by the differential maturation of sensory, neural, or motoric mechanisms important for hypodermic needle insertion versus visceral nociception.

Sex-related differences in pineal gland N-acetyltransferase induction by d-amphetamine.

The activity of the rat pineal gland enzyme, N-acetyltransferase (NAT), was measured to determine if amphetamine stimulation of norepinephrine release from sympathetic fibers innervating the gland varies according to sex-dependent mechanisms. Pineal gland NAT activity was increased following amphetamine treatment to a greater extent and for a longer duration in adult female rats compared to male animals. The greater in vivo stimulation of adult female pineal gland NAT activity by the drug developed after puberty, depended upon intact gonads, and apparently was not due to sex differences in the amount of norepinephrine released by the drug from sympathetic nerves when tested under in vitro conditions. The in vivo sex dependent effects of amphetamine may be related to the lesser rate at which the drug is metabolized and/or excreted by female rats compared to males.

Functional synaptogenesis and the rat pineal gland: a pharmacological investigation.

Pineal glands obtained from rats of different ages were incubated in vitro with drugs known to specifically alter pre- or postsynaptic noradrenergic neurotransmission to determine when during development nerve terminal or receptor mediated control of glandular N-acetyltransferase (NAT) activity might reach functional maturation. Basal daytime NAT activity measured in vitro was lowest in fetal rats, increased dramatically by the day of birth, peaked at 10 days postnatally, and subsequently declined to near adult levels by 25 days of age. Drugs (isoproterenol, norepinephrine, or propranolol) known to influence pineal gland NAT activity by acting directly on pinealocyte postsynaptic beta-noradrenoceptors produced comparable changes in enzyme activity at all ages studied, although larger doses of the receptor agonist were required in fetal animals to elevate NAT activity. In contrast, in vitro incubation with indirect acting drugs (amphetamine or 1-dopa) which require functional presynaptic nerve terminals to exert their pharmacological effects, failed to increase pineal gland NAT activity until early in postnatal life. Hence, postsynaptic beta-noradrenoceptors may function to control pineal gland NAT activity prior to the time when the presynaptic sympathetic neurons innervating the gland attain maturational status.

Diet, central nervous system, and aging.

A variety of morphological, structural, and chemical changes have been described in the central nervous systems of aging humans and animals. Brain size and volume decline during senescence, and the brain atrophy is accompanied by changes in the number, size, and ultrastructural characteristics of nerve and glial cells. Moreover, recent evidence suggests that the ability of central nervous system cells to communicate with one another via the release of neurotransmitter compounds might be impaired in the elderly. Nutritional factors may play important roles in the aging process of the central nervous system by influencing brain neurotransmission, or by accelerating or retarding geriatric changes in central nervous system structure.