The benzodiazepine partial inverse agonist Ro15-4513 alters anticonvulsant and lethal effects of carbamazepine in amygdala-kindled rats

Prenatal malnutrition-induced fetal growth retardation in the rat results in elevated arterial blood pressure at adulthood. To test the contribution of cardiovascular sensory C fibers in the hypertensive state, arterial blood pressure was measured in prenatally undernourished rats treated at birth with capsaicin. The effects of the neonatal capsaicin treatment on heart rate and respiratory frequency were also evaluated. Maternal malnutrition resulted in body and brain weights deficits in the offspring that were not modified by neonatal capsaicin treatment. Capsaicin treatment did not change the cardiovascular parameters in normal rats, but prevented the elevation of arterial blood pressure and heart rate in malnourished animals. These results indicate that elevation of arterial blood pressure in prenatally malnourished rats depends on the activity of some sensory unmyelinated C fibers.     

Neonatal capsaicin treatment results in prolonged mitochondrial damage and delayed cell death of B cells in the rat trigeminal ganglia

Capsaicin acts on the vanilloid receptor subtype 1, a noxious heat-gated cation channel located on a major subgroup of nociceptive primary afferent neurons. Following the systemic capsaicin treatment of neonatal rats, the loss of B-type sensory neurons in trigeminal ganglion of adult rats with chemoanalgesia and abolition of neurogenic inflammation was investigated. Our quantitative morphometric analysis revealed that in the trigeminal ganglion of neonatal rats treated with 50 mg/kg s.c. capsaicin, the total number of neurons, morphology of B-type cells and cell-size histograms did not differ from that of the controls 1 or 5 days after treatment. These observations indicate that early cell death does not play a significant part in the loss of B-type cells, which in our sample was 39.4% on the 19th day. However under the electron microscope pronounced selective mitochondrial swelling with disorganized cristae was observed in B-type neurons at 1-20 weeks after capsaicin treatment. Daily treatment with nerve growth factor (NGF, 10 x 100 microg/kg s.c.), started 1 day after capsaicin injection, prevented the loss of B-type cells but did not counteract the development of long-lasting mitochondrial damage. After NGF treatment, partial restitution of chemonociception to capsaicin instillation into the eye occurred but capsaicin-induced inhibition of neurogenic plasma extravasation in the hindpaw evoked by topical application of mustard oil remained unaltered. We conclude, that capsaicin treatment in neonatal rats, as in the adults, destroys terminal parts of the sensory neurons supplied by vanilloid receptors and induces long-lasting mitochondrial swelling in the soma. We hypothesize that loss of NGF uptake results in delayed cell death of B-type neurons in neonates.     

Afferent signalling through the common hepatic branch of the vagus inhibits voluntary lard intake and modifies plasma metabolite levels in rats

The common hepatic branch of the vagus nerve is a two-way highway of communication between the brain and the liver, duodenum, stomach and pancreas that regulates many aspects of food intake and metabolism. In this study, we utilized the afferent-specific neurotoxin capsaicin to examine if common hepatic vagal sensory afferents regulate lard intake. Rats implanted with a corticosterone pellet were made diabetic using streptozotocin (STZ) and a subset received steady-state exogenous insulin replacement into the superior mesenteric vein. These were compared with non-diabetic counterparts. Each group was then subdivided into those whose common hepatic branch of the vagus was treated with vehicle or capsaicin. Five days after surgery, the rats were offered the choice of chow and lard to consume for a further 5 days. The STZ-diabetic rats ate significantly less lard than the non-diabetic rats. Capsaicin treatment restored lard intake to that of the insulin-replaced, STZ-diabetic rats, but modified neither chow nor total caloric intake. This increased lard intake led to selective fat deposition into the mesenteric white adipose tissue depot, as opposed to an increase in all visceral fat pad depots evident after insulin replacement-induced lard intake. Capsaicin treatment also increased the levels of circulating glucose and triglycerides and negated the actions of insulin on these and free fatty acids and ketone bodies. Collectively, these data suggest that afferent signalling through the common hepatic branch of the vagus inhibits lard, but not chow, intake, directs fat deposition and regulates plasma metabolite levels.     

Effects on immune responses in rats after neuromanipulation with capsaicin

The effect of capsaicin treatment on the immune response, assessed as antibody formation in vivo and in vitro, was studied in ovalbumin (OA)-immunized rates. Rats were treated with capsaicin at 1-2 days of life or at adult age, before or after immunization. The levels of IgA, IgE and IgG antibodies as well as immunoglobulins were measured in serum and supernatants from cultured lymph node cells, spleen cells and peripheral blood lymphocytes. Capsaicin treatment affected the antibody levels depending on the timing of capsaicin treatment in relation to immunization. Different effects of capsaicin treatment were also observed on the different immunoglobulin isotypes. One of the most striking effects by capsaicin treatment was the reduction of IgA and IgG synthesis in cultured lymphoid cells from aerosol immunized animals treated with capsaicin after immunization. In contrast, in vivo the level of total serum IgA was increased in similarly treated animals. In this study we show that capsaicin treatment, which is known to decrease the levels of neuropeptides of sensory origin, has a time-dependent effect on both antibody levels in vivo as well as the formation of immunoglobulin in vitro. Although the mechanisms responsible for this are not obvious, we conclude a link between depletion of neuropeptides in sensory nerves and the antibody synthesis.     

Pancreatic glucagon and postprandial satiety in the rat

The hypothesis that administration of pancreatic glucagon inhibits feeding by eliciting satiety for food was tested against several behavioral and physiological criteria of specificity. The effects of intraperitoneal glucagon injections on intake of a palatable milk diet were tested in rats maintained with ad lib access to pelleted diet. Injections of 25–800 μg/kg glucagon administered at meal onset inhibited meal size by 17–36%, but did not affect the normal postprandial behavioral satiety sequence or elicit any behavioral signs of toxicity. Latency to rest and intermeal interval were not affected. Glucagon decreased meal size by specifically inhibiting feeding during the terminal phase of the meal without affecting feeding earlier in the meal. This was also the case when glucagon was injected 4 min prior to meal onset. This range of glucagon doses did not affect water intake in water deprived rats consuming fluid volumes comparable to the milk intakes. They also did not affect body temperature. Finally, injection of 400 μg/kg glucagon after the initial exposure to a novel drinking fluid was not sufficient to form a conditioned taste aversion in a two bottle preference test. These data, together with reports that circulating pancreatic glucagon levels increase during meals, strongly suggest that pancreatic glucagon is involved in the production of postprandial satiety.     

Altered lymphocyte proliferation of immunized rats after neurological manipulation with capsaicin

The neurotoxic agent capsaicin was used for depletion of the content of neuropeptides in c-fibers of the sensory nerve system in rats. The effect of the capsaicin treatment on the immune response was assessed as lymphocyte proliferation of spleen cells, stimulated with Con A. Treatment of 2 day old rat pups and adult rats did not alter the lymphocyte proliferative response to Con A in nonimmunized rats. Spleen cells from capsaicin-treated and subcutaneously immunized rats showed a decreased proliferation response to Con A. Capsaicin treatment of aerosol immunized rats did not affect the proliferation level of the spleen cells to the same extent. The results indicate that abolishment of the content of neuropeptides in the c-fibers of sensory nerves with capsaicin, affects the immune response.     

Topical versus systemic capsaicin desensitization: specific and unspecific effects as indicated by modification or reflex micturition in rats

The aim of this study was to determine the acute and delayed effect of topical application of high concentrations of capsaicin on the rat urinary bladder on micturition reflex and compare the effects of "topical" bladder desensitization with those produced by systemic (subcutaneous administration) capsaicin desensitization. On acute application, capsaicin (1-3%) produced a transient bladder contraction, not observed in capsaicin-pretreated rats. After a transient increase in excitability of the micturition reflex, topical capsaicin suppressed micturition and overflow incontinence ensued which was reverted by intravenous injection of 4-aminopyridine. Topical capsaicin also abolished reflex micturition in rats which had been systemically treated with capsaicin as adults (50 mg/kg, 7 days before) and reduced significantly the neurogenic bladder contractions produced by intravenous dimethylphenylpiperazinium or neurokinin A, while the direct (myogenic) response to neurokinin A was unaffected. In rats whose bladder was pre-exposed to 1-3% topical capsaicin (7 days before) the micturition reflex was affected in a manner which is qualitatively and quantitatively similar to that observed in rats treated with capsaicin as adults, e.g. increase in bladder capacity with no change in voiding efficiency. Topical capsaicin desensitization of the rat urinary bladder was shown to produce a selective impairment of bladder sensory nerves without any sign of desensitization in other areas of the body using both functional (hot plate, wiping, plasma extravasation) and neurochemical (determination of substance P-like immunoreactivity) assays. Systemically administered capsaicin (7 days before) had little effect on reflex micturition at 12.5 mg/kg but the change in bladder capacity produced at a dose of 25 mg/kg was comparable with that produced at 350 mg/kg. These findings provide evidence that selective desensitization of peripheral terminals of capsaicin-sensitive nerves of the rat urinary bladder inactivates their sensory and "efferent" function in a manner similar to that observed after systemic capsaicin desensitization in adult rats. The functional deficit of reflex micturition produced in this way can be overcome by increasing the stimulus to void. By contrast, neonatal capsaicin desensitization produced a long lasting abolition of reflex micturition. These data are in keeping with the hypothesis that adult versus neonatal capsaicin desensitization may be used as a tool to distinguish between two sets of sensory nerves in the rat urinary bladder.(ABSTRACT TRUNCATED AT 400 WORDS)     

In vivo lipolytic effect of glucagon in warm-adapted and cold-adapted rats.

In vivo effect of glucagon on blood-free fatty acid (FFA) concentration was investigated in rats adapted to 25 degree C and to 5 degree C. Intraperitoneal injection of glucagon in 100 or 25 mug/100 g body weight doses was followed by a triphasic response in blood FFA concentration: an immediate and marked rise at 5 min, a secondary depression at 60 min and a final rise at 120 to 240 min after the injectionss. For the 12.5 and 6.25 mug/100 g body weight injections, an initial increment was significantly lowered and no elevation at 240 min was observed. Concomitant elevations of blood glucose concentration were shown 5 min after glucagon injection of 100, 25, 12.5, and 6.25 mug/100 g body weight doses and their extents were not significantly different each other between these doses. However, rise in blood glucose level at 60 min was not seen at the 12.5 and 6.25 mug/100 g body weight doses. Blood lactate concentrations did not show any significant variations by the injections of glucagon. In fasting rats, glucagon at the 100 mug/100 g body weight dose caused similar increase in blood FFA as that in fed ones. In fed cold-adapted rats at 5 degree C glucagon at the dose of 100 mug/100 g body weight brought about similar effects in elevation of blood FFA level and its time-course as those in fed rats adapted to 25 degree C. However, under fasting condition cold-adapted animals exhibited greater increment in blood FFA level at 5 min than those adapted to 25 degree C, while an elevation of blood FFA at 240 min was not observed in the former animals. These results indicate for the first time an in vivo lipolytic action of glucagon in rats and further suggest an enhanced sensitivity to lipolytic action of glucagon in cold adaptation.     

Neonatal anandamide treatment results in prolonged mitochondrial damage in the vanilloid receptor type 1-immunoreactive B-type neurons of the rat trigeminal ganglion

Capsaicin acting on the vanilloid type 1 receptor (VR1) excites a subset of primary sensory neurons. Systemic capsaicin treatment of adult or neonatal rats results in selective damage of the B-type neurons in the rat sensory ganglia by causing a long-lasting mitochondrial lesion that has been described in detail in previous studies.The endocannabinoid, anandamide, exhibits an agonist effect on VR1 receptors. The physiological role of anandamide as a VR1 agonist is still uncertain. This study addresses whether high doses of anandamide induce similar ultrastructural changes to those described for capsaicin. The effect of neonatally administered anandamide (1 mg/kg) on neurons of the trigeminal ganglia and the hippocampal formation was examined in the light and electron microscope from the first day after injections to the 20th week after treatment. Anandamide was found to cause mitochondrial damage of the B-type neurons of trigeminal ganglia similar to what has been described for capsaicin. The time course of damage was also comparable. In addition to the cells of the trigeminal ganglia, B-type cells of dorsal root ganglia were also damaged. A-type neurons and satellite glial cells were not affected either in the trigeminal or in the dorsal root ganglia. In the hippocampal formation, where a subpopulation of local circuit neurons is known to contain cannabinoid type 1 (CB1) but not VR1 receptors, anandamide did not cause morphological changes of mitochondria either in the dentate gyrus or in Ammon's horn. At 3 weeks of age, all VR1-immunoreactive neurons in the trigeminal ganglia of animals treated neonatally with anandamide displayed swollen mitochondria.The results suggest that anandamide, at pharmacologically relevant doses, acts on the VR1 receptor and causes prolonged and selective mitochondrial damage of B-type sensory neurons, as has previously been described for capsaicin.     

Deafferentation affects short-term but not long-term control of food intake

Deafferentation affects short-term but not long-term control of food intake (PHYSIOL BEHAV XX(X) 000-000, 2005). Rats were treated neonatally with capsaicin (CAP) to investigate the involvement of vagal afferents in food intake control and body weight regulation. In the first set of experiments, rats were offered increasing concentrations of sucrose (10-15-20-40%) in short-term feeding tests of 1 h. At the end, 10% was offered again to see whether CAP rats modified their intake after repeated exposure to different concentrations of sucrose solution. Results demonstrated that CAP animals overconsume persistently compared to vehicle (VEH) controls. This overconsumption is most pronounced and variable at 10% trials. Hypertonic 40% sucrose solution resulted in a small but significant drop in intake in CAP rats. Overall, if the concentration of sucrose solution is more than 10%, sucrose ingestion of CAP and VEH rats does not depend on the concentration of sucrose solution and remains relatively constant during all trials. In another experiment, rats were exposed to a high-fat condensed milk suspension (CMS) for 5 days. CAP rats initially overconsumed from this CMS compared to VEH. This was accompanied by a decreased intake in chow. However, over the 5 day period CAP animals adjusted their CMS and chow intake to control levels. During both experiments there were no differences in body weight gain between CAP and VEH. Together, these results suggest that capsaicin-sensitive vagal C-fibers are involved in the control of volume ingestion and short-term food intake control but are not required for long-term control of energy intake.     

Epinephrine inhibits feeding nonspecifically in the rat

The hypothesis that epinephrine (EPI) and pancreatic glucagon (PG) inhibit feeding by activating a common physiological satiety mechanism was tested by comparing the two agents' behavioral effects. In several tests of specificity, EPI and PG had functionally different inhibitory actions. Intraperitoneal injection of 6.25-50 micrograms/kg EPI and 100-400 micrograms/kg PG elicited overlapping dose-related inhibitions of intake of milk diet in rats maintained ad lib on pelleted chow. Twenty-five to 50 micrograms/kg EPI also elicited anomalous behaviors that are not normally associated with feeding, including supine postures with limbs extended and crawling with trunk dorsoflexed and abdomen pressed against cage floor. EPI elicited similar anomalous behaviors in rats that either sham fed with open gastric cannulas, drank after water deprivation, or were presented neither food nor water. Fifty to 200 micrograms/kg EPI also inhibited water intake in the thirsty rats, and 25-50 micrograms/kg EPI inhibited sham feeding. PG, in contrast, neither elicited anomalous behaviors nor inhibited water intake nor inhibited sham feeding. These data demonstrate that the inhibitory actions of exogenous EPI and PG are functionally dissociable. We conclude that 25-200 micrograms/kg EPI acts nonspecifically to produce anorexia and adipsia, while PG elicits postprandial satiety.     

The effects of capsaicin on emotional responses to odors in the rat

Capsaicin is described as disturbing the autonomic responses to stress-inducing environments. The effects of capsaicin (130 mg/kg in 2 series of subcutaneous injections) on emotionality responses were studied in 19 Sprague-Dawley male rats using the open-field test. Eleven rats treated with isotonic saline served as controls. Emotionality (E) measured before capsaicin treatment in the open-field ventilated with deodorized air was similar in the 2 groups of rats. Nine out of the 19 treated rats survived. Their E was significantly higher than that of there 10 rats that died from capsaicin. When a frightening odor (fox feces) was added to the open-field E increased in the controls but remained unchanged in the capsaicin-surviving rats. The ability to discriminate palatable food or female odor was similar in the two groups. The results suggest that; 1) Highly emotional rats survived subcutaneous capsaicin injections; 2) Reaction to an emotionality-inducing environment was decreased in the capsaicin-surviving rats; 3) Olfactory discrimination was not impaired by capsaicin treatment.     

The effect of ambient temperature on rectal temperature,food intake and short term body weight in the capsaicin desensitized rat

1. .Subcutaneous injections of capsaicin (mean cumulative dose: 80.1±3.6 mg·kg^?1) permanently reduced the capacity of rats to withstand a hot environment when deprived of water. With water available, hyperthermia was discrete or absent in capsaicinized rats in hot environment.
2. Desensitization was followed by a significant decrease in both food intake and body weight. Treated rats recovered normal body weight after 3 weeks.
3. In a hot environment, compared to controls, food intake was significantly increased in capsaicin desensitized rats which maintained their body weight. In cold environment, food intake was decreased in capsaicin desensitized rats which lost body weight. At normal ambient temperature, food intake and body weight were similar in the 2 groups.
4. Caloric intake adjustment at high and at low temperatures was therefore disturbed in capsaicin desensitized rats. It is concluded that hypothalamic thermodetectors implicated in both thermoregulation and food intake behaviour could be partially damaged by capsaicin.

     

Phentolamine stimulates insulin release and glucose clearance and suppresses food ingestion

In Experiment One, phentolamine (PTA), an alpha-adrenergic blocker, was injected in rats at doses of 0, 50, 100, 200, and 300 micrograms/kg following a 4-hr fast. Measurement of food intake 1-hr postinjection revealed that 300 micrograms/kg PTA reduced food intake. Experiment Two evaluated the potential aversiveness of 300 micrograms/kg PTA. Four-hour fasted rats were adapted to a milk diet as the only food source during a 1-hr intake measurement period. After the 15-day adaptation period, three separate groups of animals (n = 8 per group) received the milk with cherry flavoring added and infections of either 1% body weight 0.9 NaCl, isosmotic LiCl or 300 micrograms/kg PTA. Only those subjects that had received LiCl injections developed a reliable aversion to the cherry-flavored milk. The final experiments subdivided the 1-hr feeding period into three 20-min segments and, in separate animals, food intake or plasma insulin and glucose changes were assessed. The animals were assigned to one of two groups receiving either 300 micrograms/kg PTA or equivolume 0.9% NaCl. PTA-injected subjects showed an immediate modest enhancement of insulin release during the first 20-min feeding segment following injection, compared to controls, while blood glucose levels decreased but never differed reliably between groups. Food intake was reliably suppressed in the second and third 20-min segments for the PTA-injected rats. We advance that PTA by enhancing glucose clearance may be reducing ingestion.     

Performance and carcass quality of swine injected daily with bacterially-synthesized human growth hormone

In this study, growth rate, feed intake, feed efficiency and carcass quality were measured in pigs (24 barrows and 24 gilts, initial body weight = 23.0 +/- 4 kg) administered 0, .015, .030 or .060 mg/kg/day bacterially produced human growth hormone (hGH) until slaughter weight of 90 kg. Administration of hGH on the first treatment day resulted in a dose-dependent peak in serum concentration after 2 hrs and concentrations gradually returned to baseline by 22 hrs after treatment. Measurement of glucose, insulin and glucagon on the first and last days of treatment showed variable effects of treatment. In pigs treated with .015 mg/kg/day hGH average daily weight gain (.89 vs .82 kg, p less than .05) and feed intake (4.59 vs 4.25 kg, p less than .006) were increased, while feed efficiencies were not different among groups. The carcass data did not show consistent differences to indicate a hGH growth response. It is concluded that hGH may be effective in pigs for improving growth rate and at doses lower than those shown effective for porcine GH.     

Capsaicin-resistant, nonspecific acetylcholinesterase (NsAchE) reactive nerve fibers in the rat cornea: a quantitative and developmental study

Little is known whether capsaicin affects on the nonspecific acetylcholinesterase (NsAchE) positive nerves in the cornea. To examine this point, the density of the corneal nerve fibers stained with NsAchE method was compared with that of control. Capsaicin (50 mg/kg) was injected once into the dorsal skin of rats at 2 day after birth. As controls, a vehicle was similarly injected into animals of the same age. At 5 (n = 3), 17 (n = 4), 45 (n = 4) and 75 (n = 3) days after treatment, the bilateral corneas were excised from capsaicin treated (n = 14) and age-matched control animals (n = 14). The entire subepithelial corneal nerves stained in whole mount preparations were hand traced. Their density was represented as mm/mm2 by converting the total areas of the nerve fibers into the total length of them using computer image analysis system. No significant differences in the nerve fiber density were seen in the control and capsaicin-treated corneas at the survival times examined. Even high doses of neonatal capsaicin injection (total: 150 mg/kg) no NsAchE-reacted corneal nerves showed a significant decrease. However, the time of wiping by instillation of 100 microM capsaicin onto the corneas severely reduced (analgesia to chemical irritant) in the neonatal capsaicin-treated rats (50 mg/kg, n = 13) compared with those of controls (n = 13) at 17, 45 and 75 day survivals. This was closely associated with the decrease of PGP-ir intraepithelial nerve fibers. The corneal nerves reacted with the NsAchE seemed to be capsaicin resistant and have a functional property except the chemical nociception.     

Acute exposure of uranyl nitrate causes lipid peroxidation and histopathological damage in brain and bone of Wistar rat.

Although the kidneys are the main target organs for uranium (U) toxicity, recent studies have shown that U can cross the blood-brain barrier to accumulate in the brain. Uranyl nitrate (U-238)induced oxidative damage was investigated in brain and bone of Wistar rats after intraperitoneal injection of uranyl nitrate at acute doses either nephrotoxic (576 microg of U/kg body weight) or subnephrotoxic (144 microg U/kg body weight). The health effects of U administration at 576 microg of U/kg body weight were seen in terms of decrease in food intake and no gain in body weight compared to respective controls. These alterations were correlated with increased lipid peroxidation as measured by thiobarbituric acid reactive substances in rat brain and bone. However, at lower dosage of U (144 microg U/kg body weight), no significant lipid peroxidation was observed in brain and bone. Histological examination of U-treated (576 microg of U/kg body weight) rat brain tissues showed marked and diffuse cystic degeneration and a similar pattern in histological alterations was observed in kidneys in treated animals; whereas no significant histological change was observed in rat brains and kidney treated with a lower dose of U (144 microg U/kg body weight). It is concluded that administration of U at an acute nephrotoxic dose caused oxidative stress in brain and bone manifested as lipid peroxidation and histopathological damage.     

Role of vagal nerve activity during suckling. Effects on plasma levels of oxytocin,prolactin, VIP,somatostatin, insulin,glucagon, glucose and of milk secretion in lactating rats

The aim of this study was to investigate the role of vagal nerve activity for the release of oxytocin, prolactin and gastrointestinal (GI) hormones during suckling as well as for the secretion of milk in lactating rats. We have therefore performed experiments on vagotomized lactating rats. The animals were decapitated and trunk blood was collected from nonsuckling rats and from suckling rats in connection with milk ejection. Oxytocin, prolactin, vasoactive intestinal polypeptide (VIP), somatostatin, insulin, glucagon and glucose levels in plasma were measured by RIA-technique. In addition, maternal weight as well as the weight of the litters were recorded 7 d after vagotomy. As expected, oxytocin and prolactin levels rose in response to suckling in sham-operated controls. In vagotomized animals the suckling-induced increase of oxytocin was blocked and prolactin levels were significantly decreased. VIP levels in plasma increased following suckling in sham-operated animals and failed to respond after vagotomy. In contrast, somatostatin levels that rose significantly in sham-operated rats were even more significantly raised in vagotomized animals. In addition, insulin but not glucagon levels were increased by suckling. The insulin response, however, persisted after vagotomy. Interestingly, suckling was followed by a lowering of blood-glucose levels in vagotomized, but not in sham-operated animals. The vagotomized rats ate as much and increased in weight as sham-operated rats during the 7 d of vagotomy. The litters of vagotomized rats, however, gained significantly less weight in comparison with control litters. In conclusion, this study shows that vagal nerve activity is of importance for the release of oxytocin, prolactin, vasoactive intestinal polypeptide and somatostatin during suckling. In addition, vagal nerve activity was found to be of fundamental importance for adequate milk secretion, since litters of vagotomized rats increased in weight less than litters of sham-operated operated animals.     

Mitochondrial DNA deletions parallel age-linked decline in rat sensory nerve function.

In rats, the function of sensory nerves in the hind limb declines significantly with age. Normally aging rats and rats treated neonatally with capsaicin were studied here. Quantification of vascular response and substance P in young (3 months) and old (24 months) rats showed additive effects of age and capsaicin treatment. The levels in dorsal root ganglion of a particular deletion in mitochondrial DNA (mtDNA(4834)) were about 300-fold higher in old compared to young rats. Capsaicin treatment had no significant effect on mtDNA(4834) abundance. Dorsal root ganglia of old (but not young) rats were found to contain a spectrum of multiple deletions. The abundance of mtDNA(4834) in dorsal root ganglia from individual rats correlated strongly with their decline in vascular function, even where vascular responses were systematically depressed due to prior capsaicin treatment. One possibility is that mitochondrial DNA mutations directly lead to functional decline at mitochondrial and tissue levels. Alternatively, loss of mitochondrial DNA integrity and physiological decline may be consequences of the same factor, such as oxidative stress.     

Body weight gain, food intake and adrenal development in chronic noise stressed rats

Wistar chronic treated rats (30 days) were used to investigate the effect of hypothalamic-pituitary-adrenal activity on growth, food intake and adrenal development (weight and DNA content). The animals were submitted to noise stress, ACTH administration and dexamethasone suppression test. Noise stress decreased body weight gain and food intake. No adrenal hypertrophy was observed but an increase in relative DNA content by stress has been found. ACTH and dexamethasone treated rats showed a body weight and food intake decrease vs. controls. The effect on body weight was higher in dexamethasone treated rats. Adrenal hypertrophy and hyperplasia were found in ACTH treated rats, whereas dexamethasone provoked adrenal atrophy with a decrease in DNA content.