Search PubMed⌕ Search

Biomedical subjects

J R Martin

Publications and source records attributed to J R Martin.

At least 145 records · Page 8Linked to original sources
PubMed1987

Modification of the development of acute opiate tolerance by increased dopamine receptor sensitivity.

Earlier studies have suggested that the acute administration of an opiate can result in the development of supersensitive dopamine receptors. The present study was undertaken to determine whether the supersensitive dopamine receptors can modify the development of opiate tolerance and dependence. Administration of morphine (100 mg/kg s.c.) 6 or 24 hr before apomorphine (i.p.) potentiated apomorphine-induced climbing behavior in mice. Administration of levorphanol (12 mg/kg s.c.) 3 or 6 hr, but not 24 hr, before apomorphine also potentiated apomorphine-induced climbing behavior. Coadministration of 5 mEq/kg of LiCl with morphine or levorphanol attenuated the increased sensitivity developed to apomorphine after either opiate. Acute tolerance and dependence was induced by administration of 100 mg/kg of morphine or 12 mg/kg of levorphanol. Lithium enhanced the development of acute tolerance when coadministered with morphine 3, 6 or 24 hr before test doses of morphine, or with levorphanol 3 hr before test doses of levorphanol. Administration of apomorphine 5 min before naloxone significantly decreased the naloxone ED50 for inducing withdrawal jumping in mice that had been pretreated with morphine or levorphanol. Although coadministration of lithium with morphine or levorphanol had no significant effect on naloxone-induced withdrawal jumping, it attenuated the ability of apomorphine to decrease naloxone ED50. Morphine (100 mg/kg s.c.) increased the number of whole brain [3H]spiroperidol binding sites 3 and 6 hr after administration of morphine. This increase was no longer present 24 hr after morphine administration. Levorphanol (12 mg/kg s.c.) also increased the number of binding sites 3 hr after administration. Coadministration of lithium with morphine attenuated the increase in [3H]spiroperidol binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Modulation of cholecystokinin release from posterior nucleus accumbens by D-2 dopamine receptor.

The effect of specific D-2 dopamine (DA) receptor agonists and antagonists on potassium (55 mM)-evoked release of cholecystokinin-like immunoreactivity (CCK-LI) was studied in tissue slices of the rat posterior nucleus accumbens (NAc). Incubating the tissue slices in 100 nM or 1 microM of LY-141865, a specific D-2 DA receptor agonist, reduced the release of CCK-LI as indicated by a significant decrease in the S2/S1 ratio. Addition of 10 microM of (-)-sulpiride, a specific D-2 DA receptor antagonist, blocked the inhibitory effect of 100 nM of LY-141865 on the release of CCK-LI. In contrast, 10 microM of the specific D-1 DA receptor antagonist SCH 23390 was unable to attenuate the decrease in release of CCK-LI caused by 100 nM of LY-141865. Furthermore, the active isomer of LY-141865, LY-171555 at 0.1 to 50 nM, also decreased the release of CCK-LI from the tissue slices, while the inactive isomer, LY-181990 at 1 nM, did not affect CCK-LI release. The inhibitory effect of LY-171555 on the release of CCK-LI was lost when its concentration was increased to 100 nM, thus revealing a biphasic effect of D-2 DA receptor stimulation on the release of CCK-LI. These results demonstrate that stimulation of D-2 DA receptor can modulate the release of CCK from in vitro slices of the rat posterior NAc.

Animals↗
PubMed1986

Chronically administered morphine increases dopamine receptor sensitivity in mice.

Chronic morphine treatment has been suggested to cause the development of supersensitive dopamine receptors. This increase in sensitivity was detected as a hypersensitivity in direct-acting dopamine agonists and as an increase in the affinity of dopamine receptors. However, these binding studies were performed in animals which had been withdrawn from morphine for a period of 24-48 h prior to killing. In the present study mice were implanted with pellets containing 75 mg of morphine free base. The pellets were left in situ in all experiments. One group of mice exhibited an increased sensitivity to apomorphine 72 h following pellet implantation as evidenced by a decrease in the ED50 of apomorphine for inducing cage climbing behavior. A second matched group of mice was found to have a significant increase in whole brain [3H]spiroperidol binding sites. These results suggest that chronic morphine treatment can cause the development of central supersensitive dopamine receptors. Lithium administered concurrently with the morphine attenuated the increased sensitivity to apomorphine and the increase in the number of [3H]spiroperidol binding sites. Concurrent lithium treatment also facilitated the degree of analgesic tolerance, and naloxone-induced withdrawal hypothermia. The ability of lithium to enhance analgesic tolerance while simultaneously attenuating the increase in dopamine receptors suggests that alterations in dopamine receptors might modify the degree of analgesic tolerance which develops to chronic morphine administration, or might modify the animal's response to thermal stimuli. The mechanism by which lithium enhanced naloxone-induced hypothermia is presently unknown.

Analgesia↗
PubMed1986

Behavioral effects of experimental portacaval anastomosis measured in Dashiell and radial tunnel maze configurations.

Male rats which had received either a surgically constructed end-to-side portacaval shunt or sham surgery were maintained on a normal diet of laboratory chow or on chow plus a low tryptophan, low protein supplement. In 6-min long daily tests carried out in both a Dashiell and a radial tunnel maze configuration for 6-day blocks, numerous behavioral parameters were automatically registered via a computer-interfaced maze system. The dietary condition failed to affect the activity level of the two surgical groups. After collapsing the behavioral data across dietary condition, discriminant analysis yielded two significant factors which were subsequently found to differentiate the two surgical groups: the intrasession habituation of locomotion and the total activity within a session. The rate of intrasession activity decline was significantly more rapid for portacaval-shunted rats than their surgical controls, but only in the Dashiell configuration. The control rats exhibited significantly greater total activity during evaluation in the radial maze; whereas in the Dashiell configuration the total activity of the portacaval-shunted rats was higher than controls only during the first few days but lower during the final few days of testing. These results indicate that, depending upon the maze configuration, spontaneous locomotor activity and the decline of activity within a test session were altered in the rat with portal-systemic shunting of the circulation, which has been proposed as an animal model of chronic liver dysfunction.

Animals↗
PubMed1986

Central nervous system and genital infection with reactivation of latent herpes simplex virus type 2 in mice.

To establish a reactivation model of genital and central nervous system infection, 3- to 12-week-old outbred or BALB/c mice were inoculated vaginally with the HG-52 strain of herpes simplex virus type 2 (HSV-2). Primary infection was confirmed by serially positive vaginal cultures. Mortality in 6- and 12-week old infected mice was about 20%. In survivors, clearance of infectious virus was confirmed in serially negative vaginal cultures. At 6 weeks, immunosuppression of survivors with cyclophosphamide and antilymphocyte serum was begun. Recurrent virus shedding, monitored by daily vaginal cultures, was detected in the majority of animals. All mice became moribund or died, usually during the third to fifth weeks of immunosuppression. Brains and spinal cords from which all sensory ganglia had been removed were homogenized and inoculated onto cultures. One or both central nervous system (CNS) samples were virus-positive in nearly half of these mice, and cell-free virus was isolated from most positive brain and cord supernatants tested. Three-fourths of mice had evidence of virus reactivation with immunosuppression, as indicated by vaginal or CNS isolations, and by failure to isolate virus by identical means in matched infected, non-immunosuppressed controls. Vaginal, spinal cord and brain isolates occurred independently of one another in many immunosuppressed mice, and could not be predicted from presence or absence of external genital lesions during primary infection. These experiments show that with immunosuppression, reactivations of latent HSV-2 infections in mice can be detected in the genital tract and CNS, and provide a model to study productive, recurrent CNS infection and disease.

Animals↗
PubMed1986

Discordant motor activity levels of portacaval-shunted rats in runway and swim tests.

Male rats received an end-to-side portacaval anastomosis (PCS) or sham surgery and were permitted to recover from the acute effects of surgery. The motor activity of PCS and sham rats was measured for a 63-min period in an enclosed runway during both diurnal and nocturnal phases and on two different dietary regimens. PCS rats were less active than sham controls under all experimental conditions; neither time of testing nor addition of corn to the usual laboratory chow diet significantly influenced motor activity. In a subsequent test, PCS and sham rats received repeated trials in a swim canal until exhaustion occurred. There was no significant difference between these two groups in either the number of swim trials completed or the total time spent swimming up to the final trial. These latter results suggest that the activity deficit observed in PCS rats in the runway test was probably not a consequence of early exhaustion or fatigue.

Animals↗
PubMed1986

Altered light/dark activity difference with aging in two rat strains.

The daily activity rhythm of adult and senescent male rats of two different strains (Iva:SDIV and Emd:Wi-AF/Han) was evaluated over several days with a capacitance-induction motility monitor. The Iva:SDIV rats were 6 to 9 or 29 to 32 months old and the Emd:Wi-AF/Han rats were 3 to 5, 16 to 18, or 31 to 39 months old at the time of testing. The rats were maintained in individual cages under a 12:12 hr light/dark regimen prior to and during this experiment. Senescent rats were much less active during the dark phase and somewhat more active during the light phase than same-strain young adult rats. This pattern of results was found for measurement of gross and fine movements combined (high sensitivity setting) and to a lesser extent for gross movements alone (low sensitivity setting). Furthermore, in the senescent rats the absolute magnitude of the light/dark activity difference was found to be positively related to the subsequent survival time.

Aging↗
PubMed1986

Avoidance acquisition in adult and senescent rats.

Male rats aged 6, 19, or 33 months were trained successively in one- and two-way avoidance tasks. The one-way avoidance test consisted of up to 30 trials given in a single session with the conditional stimulus (CS; 14-kHz tone) presented for either 3 s or for 10 s in separate groups. Senescent rats performed poorest, middle-aged rats intermediately, and young adult rats best. Failure of the longer CS to yield better acquisition than the short CS in the senescent group suggested that the age-related deficit probably did not result from slower responding. In subsequent shuttle box training there was no appreciable age difference in achieving the learning criterion. A compound visual-auditory CS was used, and in further evaluation of well-trained rats it was found that the auditory component was much more effective than the visual component in eliciting avoidance. However, this differential effect of the two stimuli was much weaker in the senescent group than in the young adult group. Nonetheless, these same senescent and adult rats readily learned to make avoidance responses using only the auditory CS, demonstrating that this was an effective stimulus for all age groups.

Aging↗
PubMed1985

Increased sensitivity to dopamine agonists following a single dose of morphine or levorphanol in mice.

Acute administration of an opiate has been suggested to result in the development of supersensitive dopamine receptors. This hypothesis was tested in mice by determining the effect of a single administration of morphine or levorphanol on dopamine agonist-induced stereotypic behaviors and [3H]spiroperidol binding. Administration of morphine (1.0 mg/kg s.c.), which itself had no significant effect on spontaneous locomotor activity 3 h following administration, significantly potentiated locomotor activity induced by 1.5 or 4.5 mg/kg of apomorphine (i.p.) administered 3 h later. Morphine (10 mg/kg, s.c.) or levorphanol (0.2 and 2.0 mg/kg, s.c.), but not dextrorphan (up to 20 mg/kg, s.c.), enhanced climbing behavior induced by apomorphine (i.p.) or (-)-N-n-propylnorapomorphine (i.p.; NPA) administered 3 h later. An increase in whole brain and striatal [3H]spiroperidol binding sites was found 3 h after administration of 10 mg/kg of morphine. Concurrent administration of 5 mEq/kg of LiCl (i.p.) or 5 mg/kg of naloxone (i.p.; administered twice) attenuated both the potentiation of the climbing behavior induced by the two dopamine agonists and the increase in [3H]spiroperidol binding sites. These results suggest that a single administration of an opiate can induce the development of supersensitive dopamine receptors that is mediated by an interaction at opioid receptors.

Animals↗
PubMed1985

Effects of tunnel maze complexity on caffeinic hyperactivity in the rat.

The study investigated effects of caffeine on spontaneous tunnel locomotion without consummatory reward. The stimulant effects consisted in delayed intrasession habituation, and they differed in magnitude according to dosage and the complexity of the tunnel arrangements. In a simple hexagonal tunnel without choice points, 16 mg/kg BW produced greater stimulation than other doses, and this most efficient dose became less effective if tunnels were arranged according to the radial maze paradigm. No stimulation was obtained if an open field was incorporated into the maze. Caffeine also had no effect on open field behavior, but it tended to improve the efficiency of radial arm maze patrolling, and its significantly depressed exploration of short tunnel arms branching from the radial arms in favor of exploration of the more distant radial tunnel ends.

Animals↗
PubMed1985

Drug induced hypothermia in adult and senescent rats.

Temperature regulation was evaluated in senescent (34-40 month old) and adult (8-9 month old) female Iva:WIWU and Emd:Wi-AF/Han rats. Injection of 1.5 mg/kg BW apomorphine HCl or 1.0 mg/kg BW oxotremorine sesquifumarate produced comparable maximal hypothermic responses in adult and senescent rats. However, the latency to reach maximal hypothermia after oxotremorine (but not apomorphine) was longer in senescent than in adult rats of both strains.

Aging↗
PubMed1985

Drinking by senescent and adult rats in response to regulatory challenges.

The regulation of water and electrolyte balance was elevated in senescent (greater than 31 months) and adult (5-10 months) rats of several strains. Weekly food and water intake, drinking induced by 24-hr water deprivation and drinking induced by injection of hypertonic saline were roughly the same in old and adult rats. However, senescent rats drank less after injection of the beta-adrenergic agonist isoprenaline than adult rats. There were no appreciable strain differences in drinking in response to these regulatory challenges although baselines sometimes differed between strains.

Aging↗
PubMed1985

Uptake, accumulation, and egress of erythromycin by tissue culture cells of human origin.

The ability of erythromycin A base to penetrate and accumulate in tissue culture cells of human origin was investigated. The antibiotic was highly concentrated by early passage cells of normal bronchus, kidney, liver, lung, and skin and by cancer cells derived from breast, liver, and lung. Intracellular levels 4 to 12 times that of the extracellular milieu were obtained in both early-passage and transformed cells. The total quantity of erythromycin accumulated depended on the extracellular concentration of antibiotic, but the cellular/extracellular ratios were, for the most part, independent of the initial extracellular drug concentration. In all cell types tested, the accumulated antibiotic rapidly egressed when cells were incubated in antibiotic-free medium. Bioactivity assays demonstrated that the expelled drug was unmetabolized, fully active antibiotic. The concentration of erythromycin by a variety of human cell types probably accounts, in part, for the effectiveness of the antibiotic against intracellular parasites such as Legionella and Chlamydia spp.

Cells, Cultured↗