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UNLABELLED The calcium channel blocker nifedipine has analgesic properties that are enhanced by nicotine. Although it is not known how this analgesic state might affect the awareness of anginal pain and impending myocardial infraction, recent studies have shown an increased mortality associated with the use of large doses of nifedipine. Because both nifedipine- and nicotine-induced analgesia involve serotonergic mechanisms, we studied the effects of the serotonin biosynthesis inhibitor parachlorophenylalanine (pCPA) on nifedipine- and nicotine-induced analgesia. Nociception was assessed by tail-flick method. Rats pretreated with pCPA (300 mg/kg intraperitoneally [IP]) followed by either nifedipine (15 mg/kg IP) or nicotine (1 mg/kg subcutaneously) had a increase in tail-flick latency of 41% (P = 0.09) and 50% (P = 0.05), respectively, compared with animals that did not receive pCPA. Additionally, rats pretreated with pCPA followed by a combination of nicotine and nifedipine doubled their tail-flick latency (P = 0.0001) compared with animals that were not treated with pCPA. These data further support the involvement of the serotonergic system in both nifedipine- and nicotine-induced analgesia and suggest that drugs that affect serotonin levels, including tricyclic antidepressants and serotonin-specific reuptake inhibitors, may also affect the analgesia induced by nifedipine and nicotine. IMPLICATIONS This study examines the effect of serotonin depletion on nicotine- and nifedipine-induced analgesia. Nifidipine is a calcium channel blocker used to treat high blood pressure. It also has pain-relieving properties that are enhanced by nicotine. Because both nifedipine- and nicotine-induced analgesia involve the neurotransmitter serotonin, it is important to know how changes in serotonin concentration might affect both nicotine- and nifedipine-induced analgesia. This study not only supports the involvement of the serotonergic system in both nifidipine- and nicotine-induced analgesia, but also suggests that drugs that affect serotonin levels may also affect analgesia induced by nifidipine and nicotine.

We explored the relationship between antinociceptive and hypotensive effects of nifedipine (NIF) injected intraperitoneally (ip, 15 mg/kg) and epidurally (epi, 20μM), as compared to verapamil (VER, 10 mg/kg ip) and nitroglycerin (NTG, 0.1 and 0.15 mg/kg ip).The systolic blood pressure (BP) and tail-flick (TF) latencies were measured simultaneously every 10 min for 2 hours and individual values of both measurements were correlated. The highest antinociceptive as well as hypotensive effects were both measured in the group receiving NIF epi., with the correlation coefficient r 2 = 0.2878. Injected ip., NIF revealed similar antinociceptive effect, whereas the other studied drugs were not effective. As to the degree of hypotensive activity, NIF epi was followed by VER, NTG 0.1, NIF ip. and NTG 0.15. No significant correlation was found between BP and TF latencies in any group receiving the drugs. We concluded that the antinociceptive response, measured by the tail-flick technique, is independent of the hypotensive activity of the studied drugs, including NIF.

The purpose of this study was to determine whether ondansetron (OND) has local anesthetic effects. Using a patch-clamp technique, we showed that OND concentration dependently blocked Na channel currents in freshly isolated neurons of rat brains with a 50% inhibition concentration of 12 microM. The blockade started immediately when OND was applied to the cell body using a fast perfusion system, reached a plateau within 15 s, and recovered to the control level within 30 s after washout of the OND-containing solution. Because this is a known property of local anesthetics, we used the tail-flick technique to verify this effect in vivo in Sprague-Dawley rats (n = 46). OND was injected subcutaneously into the tail at the doses of 0.08, 0.16, and 0.2 mg. The tail-flick latency increased 2 min after OND injection, reaching the plateau within 5 min. This effect was dose-related, lasting from 10 to 25 min. These preliminary data indicate that OND, a selective 5-HT3 receptor antagonist, might serve as a prototype molecule for development of a novel series of local anesthetics.Ondansetron is a drug used to prevent vomiting, especially in cancer patients after chemotherapy. We found that it also causes numbness when injected under the skin. This new action may contribute to its role in "calming the stomach." We studied the effect of ondansetron on the isolated brain cells of live rats.

Patients with reflex sympathetic dystrophy (RSD) often present with pain and disability that cannot be explained on the basis of objective physical findings. This has led some to speculate that RSD may be caused or mediated by non-organic factors. Unfortunately, there have been few studies using standardized measures of mood and illness behavior that have compared patients with RSD to patients with other chronic pain disorders. The goal of the present study, therefore, was to compare the pattern of psychological dysfunction in patients with RSD to the pattern of dysfunction in patients with chronic back pain and local neuropathic pain. Patients with back pain resemble those with RSD in that both may report symptoms that cannot be reconciled with objective physical findings. Patients with local neuropathy, by contrast, report pain that is both circumscribed and consistent with a known organic cause. The records of 253 patients attending a tertiary pain service were retrospectively reviewed and three distinct (non-overlapping) diagnostic groups were formed: 25 were assigned to the RSD group; 44 to the back pain group; and 21 to the local neuropathy group. Using a set of stringent criteria to diagnose RSD and an analysis of covariance to control for differences in symptom duration and age, the present study found no evidence to suggest that patients with RSD were psychologically unique. Instead, RSD patients were remarkably similar to those with local neuropathy in terms of their symptom reporting, illness behavior, and psychological distress. The only exception was that RSD patients had more disability days during the preceding 6 months than those with local neuropathy (P < 0.05). The back pain group, on the other hand, presented with more diffuse pain complaints (P < 0.05) and had a greater number of non-specific medical symptoms (P < 0.05) compared to either the RSD or local neuropathy group. In contrast to previous research using less stringent diagnostic criteria, there was no evidence of higher pain scores or lower levels of psychological distress among patients with RSD. In addition, a validated survey of childhood trauma found that sexual abuse, physical abuse, emotional abuse, and cumulative trauma were evenly distributed among all three diagnostic groups. The burden of proof would appear to be upon those who advocate the non-organic hypothesis to provide credible evidence of psychological involvement in the etiology of RSD.

Antinociceptive effect of nifedipine (15 mg/kg i.p.) and verapamil (10 mg/kg s.c.) was examined in rats chronically exposed to nicotine (6 mg/kg/day via Alzet osmotic pump for 28 days) and after nicotine withdrawal. Sham operated rats served as control for testing DMSO (dimethylsulfoxide, a solvent for nifedipine), nifedipine and verapamil alone. Nociception was measured by the tail-flick technique. Nifedipine, but not verapamil, injected to control rats produced a ceiling tail-flick latency (20 sec) 30 min after the injection, lasting for 10 min. In rats exposed to chronic nicotine for 3 days, nifedipine treatment exhibited ceiling tail-flick latency within 10 min lasting for 80 min. Tested in rats exposed to nicotine for 3 weeks, nifedipine treatment produced this effect 25 min after the injection lasting for 60 min. Nicotine withdrawal abolished this effect. Verapamil did not exhibit any significant changes in tail-flick latencies. These data support our hypothesis that smoking patients treated with nifedipine could be at a potential risk in developing a high pain threshold and missing the first sign of heart attack -a chest pain.

We examined the modulatory effect of nifedipine (NIF, 0.04, 2, 5 and 15 mg/kg i.p.) and verapamil (VER, 2.5 and 10 mg/kg s.c.) on nicotine-induced antinociception in male rats, employing the tail-flick (TF) test. All rats were divided according to their responses to nicotine (1 mg/kg s.c.) alone, and classified as responders and nonresponders; both types were used. Both tested drugs were injected simultaneously with nicotine (NIC). In responders , NIC (1 mg/kg s.c.) alone produced a ceiling TF latency (15 sec) within 2.5 in lasting for 2.5 – 7.5 min. NIF, at the dose of 15 mg/kg i.p., prolonged this effect up to 40–50 min. Lower doses (5, 2 and 0.04 mg/kg) were not effective. VER in either dose did not prolong NIC-induced antinociception. In nonresponders , NIF also potentiated NIC-induced antinociception, and this effect appeared to be dose-related, lasting from 10 up to 40 min. VER was ineffective in either dose. These data support our hypothesis that calcium is involved, at least in part, in nicotine-induced antinociception. The potential risk for smoking patients treated with NIF is discussed.

The tail-flick (TF) technique was used to assess the antinociceptive properties of nifedipine (NIF) given intraperitoneally (i.p.). First, the most suitable intensity of the noxious stimulus (temperature of the bulb) has been ascertained and used in the main study. Male Sprague-Dawley rats received NIF, dissolved in dimethyl sulfoxide (DMSO) at the doses of 0.0, 0.5, 2, 5, 10 and 15 mg/kg, or control with no injection. For the main study, the noxious stimulus was limited to 15 sec (cut-off time) and TF latencies were recorded up to 120 min. The antinociceptive response was expressed as the area under the curve for each rat and analyzed by one-way ANOVA. The antinociceptive response to the lower doses of NIF (0.5 and 2 mg/kg) did not differ from control (no injection) and DMSO alone. Significance was found at 5, 10 and 15 mg NIF with no difference among the doses. However, there was an increasing tendency of the mean values from 0.5 to 15mg NIF resulting in a positive correlation. The correlation coefficient was 0.32483 (p=0.015) and regression equation Y=(19.37) × dose + 1320. Our data suggest that spinal mechanisms are involved in NIF-induced antinociception.

The serotonergic system is involved in pain transmission and the 5-hydroxytryptamine (5-HT3) receptor subtype mediates some of these effects at the spinal level. Therefore, we explored the effects of the serotonergic system on nifedipine-induced analgesia by using the 5-HT3 receptor antagonist ondansetron. Male Sprague-Dawley rats were pretreated with ondansetron (1 mg/ kg intraperitoneally) or normal saline. After 15 min, rats received injections of nifedipine (15 mg/kg intraperitoneally) or dimethylsulfoxide (DMSO), solvent for nifedipine, as a control. Nociception was assessed by tail-flick method. Rats treated with nifedipine alone had an increase in tail-flick latency of 122%, as measured by the area under the curve, compared to rats treated with DMSO alone. Pretreatment with ondansetron, however completely blocked the analgesic effect of nifedipine, with tail-flick latency remaining at baseline throughout the measurement period. These results indicate that the 5-HT3 receptor plays an important role in the analgesic response to nifedipine and that medications that block this receptor may decrease the analgesic effectiveness of this type of therapy.

Rats, pretreated with saline or GABA A antagonist bicuculline (BIC) at the doses of 2, 4, 6, 10 and 20 mg/kg, were injected with nicotine (NIC, 1mg/kg) 30 min later. Tail-flick (TF) latencies were measured before (baseline) and three times at 10 min interval after pretreated compounds, continued every 10 min up to 1 hr after NIC injection. In all groups, median TF latencies did not change from the baseline for the first 30 min after the pretreatment. Following NIC alone (control) and in the group pretreated with 2 mg/kg BIC, 60% rats reached ceiling TF latencies (20 sec) lasting for 10 min. In groups with higher BIC doses (4 to 10mg/kg), median TF latencies were in the range of 5–7 sec with 30% rats reaching the ceiling TF latencies. Following 20mg/kg BIC, one out of five rats reached 20 sec; the median was in the range of 4–5 sec. Significantly lower responses were observed following 4mg BIC and higher doses with no difference among the groups. In conclusion, our novel data show that BIC alone, injected systemically, does not possess any effect on the thermal nociceptive transmission as measured by the tail flick test. However, pretreatment with BIC partially prevents NIC-induced antinociception, in a non dose related manner. This suggests that GABA A receptors may, at least in part, contribute to the complex mechanisms involved in NIC-induced antinociception. © 1997 Elsevier Science Inc.

While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (IGABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on IGABA. That is, high concentrations (100 microM-40 mM) decreased and lower concentrations (0.01 microM-0.001 microM) potentiated IGABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect on IGABA. Finally, when 0.001 microM BDM, 10-30 microM PTX and GABA were co-applied the inhibitory effect of the toxin on IGABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.

We explored the analgesic effect of epidural nifedipine in male Sprague-Dawley rats. By using an implanted epidural catheter, the rats were given 35 microL of dimethylsulfoxide (DMSO) alone or DMSO containing 2.5, 5, 10, or 20 microM of nifedipine. Analgesia was measured by tailflick (TF) involving spinal reflexes, and by hotplate (HP) requiring an intact central nervous system. The latencies were recorded up to 120 min after the injection. The cutoff time of the noxious stimuli was 20 s in the TF and 60 s in the HP to prevent tissue damage. The TF technique revealed a significant difference from the control at doses of 5, 10, and 20 microM with no difference among the groups. Maximum latencies (cutoff time) lasted for 15, 30, and 40 min at doses of 5, 10, and 20 microM, respectively. The HP technique disclosed a dual effect: a significant decrease at the dose of 2.5 microM, no effect at 5 microM, and an increase at 10 and 20 microM. However, the median latency did not reach the cutoff time. We conclude that nifedipine, given epidurally, possesses antinociceptive properties at the dose of 5 microM and higher, detected better by the TF than HP. Our data suggest that the antinociceptive effect of nifedipine, at the studied doses, is more prominent at the spinal than the supraspinal level.

The involvement of calcium in nicotine-induced analgesia in male rats was explored using the tail-flick test. A single dose of nicotine (1 mg/kg SC) produced a maximal effect on tail-flick latency (15 s) within 8-10 min, which lasted for 4 min. Pretreatment with the calcium chelator, EDTA (250 microM/kg SC four injections at 15 min intervals), before the single dose of nicotine accelerated the onset and prolonged the duration of the nicotine-induced analgesia. The maximal effect on tail-flick latency occurred within 2 min and lasted for 10-20 min. Conversely, pretreatment with calcium chloride (1.5 mM/kg IP) attenuated nicotine-induced analgesia. It is suggested that nicotine may exert its antinociceptive effects via modulation of calcium fluxes across the neural membrane.

Following a single dose of nicotine, (NIC, 1 mg/kg s.c.), 60% of tested rats revealed significant antinociception as measured by the tail-flick (TF) test, and were classified as responders, with those in which TF latencies did not change, nonresponders. The following experiments were carried out one week later. In nonresponders, pretreatment with ethylenediaminetetraacetic acid (EDTA, 250 microM/kg s.c. four times every 15 min) followed by 1 mg NIC, produced significant analgesia in 50% of rats, to the same magnitude as did nicotine alone (1 mg) in responders. The other 50% of rats which failed to respond to EDTA pretreatment, all revealed similar analgesia following the higher dose of NIC (1.5 mg/kg s.c.), with similar side effects, as generally observed in responders. In responders, pretreatment with CaCl2 (1.5 mM/kg s.c.) completely abolished NIC (1 mg/kg s.c.)--induced analgesia in all rats. Our data provide stronger evidence and a further verification that EDTA potentiates, whereas CaCl2 completely abolishes, nicotine-induced analgesia in rats; supporting our hypothesis of the involvement of calcium ions in this effect.

Nicotine (6 mg/kg/day) was administered subcutaneously via Alzet osmotic pumps to rats for 28 days. Nociception was measured by the hot-plate and tail-flick methods. A significant antinociceptive effect was demonstrated during the first week of the treatment; after that tolerance developed, lasting for the remaining period of nicotine treatment. This effect was more pronounced in the habituated, rather than in the naive, rats. Rats subjected to nicotine withdrawal tended to exhibit the nociceptive effect for 10 days with an overall P value on the border of significance. This chronic nicotine-induced antinociception and nicotine withdrawal-induced nociception was detectable only by hot-plate but not the tail-flick technique.

We had previously shown that the hypothalamo-neurohypophyseal vasopressin secreting system is suppressed in aged rats. In the present study, using aged (26 months) male Fischer 344 (F344) rats, we showed that in contrast to vasopressin, oxytocin plasma concentration and hypothalamic content were unaltered in comparison with young (2-3 months) rats; however, based on data from our past and current studies, the neurohypophyseal concentrations of both hormones were found to be decreased in aged rats. We also compared the effect of aging on the oxytocin and vasopressin in secretory functions. Superfusion technique was employed to examine oxytocin and vasopressin release from isolated neural lobes of young (2-3 months) and old (26 months) male F344 and young (2-3 months), middle-aged (12 months) and old (30 months) Sprague-Dawley (SD) rats. Aging affected basal release of oxytocin and vasopressin in a differential manner. Expressed per gland, basal release of oxytocin increased in aged rats of both strains; whereas vasopressin release decreased in SD, and did not change in F344, old rats. The vasopressin responses to electrical stimulation, 56 mM K+ and initial traumatic release were decreased in aged rats; whereas oxytocin responses were either unaltered or decreased much less. All age-related changes were more pronounced in SD than in F344 rats. Thus, while the aging process is associated with a significant impairment in the vasopressin secretory function, the oxytocin secretory function is much less affected by that process. Significant strain differences were observed in the effects of aging on oxytocin and vasopressin release.

The effect of aging on vasopressin (VP) clearance was studied in male Fischer 344 rats 2 (young), 12 (adult) and 30 (old) months of age using in situ liver perfusion technique. The liver was perfused with Krebs-Henseleit bicarbonate buffer containing 1% bovine serum albumin and VP (2 ng/ml), at a constant temperature of 37 +/- 0.5 degrees C and a flow rate of 150 ml/h for 120 min. Expressed per whole liver and per gram tissue, VP declined exponentially over the studied period fitting well to the curve y = bekx (p = 0.0001) in all three groups. The analysis of covariance revealed the slope of the VP decay curve to be steepest in old rats, significantly different from that of young (p = 0.0001 expressed per whole liver or per gram tissue) and adult (p = 0.0001 and p = 0.001, expressed per whole liver and per gram tissue, respectively) rats. This suggests that, at least in male Fischer 344 rats, the hepatic clearance of VP was fastest in old rats.

Radioimmunoreactive vasopressin was measured in plasma, neurohypophysis and hypothalamus of the rats after different procedures of killing: a) microwave irradiation; b) decapitation; c) decapitation following a stress induced by immobilization in a restrainer. Vasopressin content in the neurohypophysis and hypothalamus was much lower in microwave irradiated than in both decapitated and stressed decapitated rats. In addition, the data from microwave technique were inconsistent with a large scatter. Plasma vasopressin concentration was elevated in both the microwave irradiated and stressed decapitated rats, demonstrating that restraining of the animals induced an excessive stress. Microwave irradiation technique including the necessary manipulation of the animal proved to be less suitable than decapitation technique for the measurement of vasopressin. It is likely that vasopressin in the hypothalamus and neurohypophysis is relatively resistant against post-mortem proteolysis.

We studied the effect of aging on vasopressin (VP) release from isolated neurohypophyses (NH) individually superfused with synthetic medium TC 199 with Hanks' salts. The superfusion technique is described in detail. Male Fisher 344 rats 2 months (young, n = 17), 12 months (adult, n = 14) and 30 months (old, n = 17) of age were used. VP was measured by radioimmunoassay (RIA). The age-related VP release was analyzed as follows: initial traumatic release, basal release, VP release evoked by electrical stimulation (10-second trains every 20 s of matched biphasic stimuli, 0.2 ms width, 8 mA, 30 Hz), by chemical stimulation (56 mM K+) and total release for the entire superfusion period. When VP release was expressed per milligram NH, it was significantly lower under all conditions in the old rats than in the young ones. In the adult rats, traumatic, basal and total release values were similar to those of the young rats, whereas their responses to chemical and electrical stimulation were similar to those of old rats. Residual VP content expressed per whole NH was significantly higher in the old and adult rats, reflecting a larger glandular size, but when expressed per milligram NH tissue, it was low in the old rats. The percent of VP released during the entire superfusion period relative to the residual VP content was significantly lower in the old than in the young and adult rats. The magnitude of the maximal VP release exceeding the basal release, in response to electrical and chemical stimulation, was similar in young and old rats. However, in the adult rats it was significantly lower than in both the young and old following chemical stimulation. A significantly larger number of old and adult NHs exhibited a more delayed response to chemical, but not to electrical stimulation, than did the young NHs. These data demonstrate an age-related decrease in VP release in Fisher 344 rats. Since the traumatic and basal VP release in the adult rats is similar to the release in the young rats, while the stimulated release in the adult rats resembles the response of the old animals, the results suggest that an impairment of stimulated VP release occurs at an earlier stage of the aging process than does an impairment of spontaneous (traumatic and basal) release.

Laser photobiostimulation (LPBS) at the pulsing frequency of 4 Hz applied to the low resistance point located at the base of the tail of the rat, (Governing Vessel Meridian 1), produced a hypoalgesic effect, measured by tail-flick and hot-plate techniques. Pre-treatment with low dose naloxone (2 mg/kg) did not reverse the hypoalgesic effect of LPBS. High dose naloxone (20 mg/kg) reversed only partially, but significantly, the hypoalgesic effect of LPBS measured by hot-plate, but not that measured by the tail-flick technique. These data suggest that mechanisms other than endogenous opioids may be involved in LPBS-induced hypoalgesia.

Plasma vasopressin (VP), serum and urine osmolality (Sosm, Uosm), serum and urine electrolytes (Na+, K+), cardiac index, and arterial pressure were studied before, during, and after cardiopulmonary bypass (CPB) in 27 patients. Of these, 13 underwent coronary artery bypass (CAB), seven underwent aortic valve replacement (AVR), and seven underwent mitral valve replacement (MVR). During CPB, plasma VP concentration rose significantly in all three groups. The CAB group showed the highest average increase in plasma VP concentration during CPB over the preinduction values, an increase significantly higher than that in the valve groups (p

Vasopressin (VP) was measured by RIA in the plasma, neurohypophysis (NH) and hypothalamus (HT) of young (2 months), adult (12 months) and old (30 months) male Fisher 344 rats, ten of each age. Plasma VP concentration was significantly lower in old compared to adult and to young rats. VP content in the NH expressed per mg weight was similar in all three groups, while the hypothalamic VP content was decreased in the aged rats. This suggests that reduced synthesis and release and/or increased degradation of VP occurs in aged rats. These data are in an agreement with our previous results obtained with Sprague-Dawley rats indicating that these differences are not strain-related. In a pilot experiment, we further studied VP release from isolated perifused NH of young and old rats. Two glands of each age were simultaneously perifused in individual microchambers with medium TC 199 and subsequently stimulated by Locke's medium containing 56 mM K+. Both, the initial and the basal VP release from the NH of the old rats, as well as the response to high K+, were about a half that of the young rats. Thus, a decreased VP release may contribute to the findings of lower plasma VP concentration in aged rats.

We demonstrated a 50% increase in pain threshold following laser photobiostimulation (LPBS), employing rat tail-flick test. Helium-neon laser (1 mW) of three different pulsing frequencies (4, 60, and 200 Hz) was applied on tail low resistance point for 15 seconds and tail-flick latencies were measured 30 minutes, 1 hour, 24 hours, 48 hours and 7 days later. LPBS of 4 Hz produced hypoalgesia of rapid onset and short duration while the response to 60 Hz was delayed and lasted longer. LPBS of 200 Hz did not produce any hypoalgesia.

We studied the effect of aging on the decline in vasopressin (VP) release from the rat neurohypophyses (NH) as evoked by repeated stimuli with high K+ (56 mM) Locke's solution in vitro. Isolated NHs, without pars intermedia, of 2-, 12- and 30-month-old male Fisher 344 rats arbitrarily labeled as young, adult, and old were individually superfused with synthetic medium TC 199. Following the initial traumatic release, the glands were stimulated three times for 10 min each with recovery periods of 35 min between stimulations. VP was measured by radioimmunoassay. Expressed per mg NH, basal VP release in the old rats, and stimulated VP release in both the adult and old rats, was decreased. The gradual decline (slope) of VP release following subsequent stimuli with high K+ was proportional, however, in all age groups. Thus, decreasing response of VP release to repeated stimulation is a function of the initial response but is not age related. These findings suggest that only some components of the chain of events involved in the release mechanisms are impaired in aging animals, whereas others may remain unaffected.

Immunoreactive vasopressin (VP) was measured in the plasma, neurohypophysis (NH) and hypothalamus (HT) of young (3 months), adult (12 months), and old (30 months) Sprague-Dawley male rats, both intact and anesthetized with halothane. VP content in the HT of the old rats was about half that of young and adultsrats. Total VP content in the NH increased with age, reflecting large glandular size in the old rats. However, VP content was similar in all three groups, when expressed per mg of wet tissue. Plasma VP concentration was undetectable in the old intact rats and it rose to the levels of intact young or adult rats during halothane anesthesia. The anesthesia-related increase in plasma VP concentration was statistically significant in young but not in adult rats. These results suggest that in the intact rats during aging: (1) the synthesis of VP in the HT may be reduced; (2) the storage of VP in the NH is not impaired; and (3) the undetectable plasma VP concentration may reflect either reduced VP release or increased degradation.