Biomedical subjects

S L Dalterio

Publications and source records attributed to S L Dalterio.

11 recordsLinked to original sources

PubMed1987

Acute delta 9-tetrahydrocannabinol exposure alters Ca2+ ATPase activity in neuroendocrine and gonadal tissues in mice.

Acute administration of delta 9-tetrahydrocannabinol (THC) (50 mg/kg) at puberty (35-40 days) significantly (P less than 0.05) reduced Ca2+ ATPase activity in hypothalamic plasma membranes but increased, although not significantly, enzyme activity in hypothalamic tissue obtained from adult mice. In contrast, testicular Ca2+ ATPase activity was increased in pubertal THC-treated males, and significantly reduced in adults. Pituitary Ca2+ ATPase activity exhibited a dose-related decrease after acute THC administration at 0.5, 5 or 50 mg/kg, but there were no differential effects of age. Pituitary plasma membranes obtained from THC-treated males did not respond to in vitro exposure to luteinizing hormone releasing hormone (LHRH, 10(-7) M) with the marked reduction (approximately 40%) in Ca2+ ATPase activity observed in pituitaries from oil-treated controls. In addition, effects of THC appear specific for Ca2+ ATPase activity, since Mg2+ ATPase and Na+/K+ ATPase activities were not affected. These findings indicate that acute in vivo administration of THC influences Ca2+ membrane transport, in particular Ca2+ ATPase activity. These effects occur at each level of the hypothalamic-pituitary-gonadal (HPG) axis, are related to dose and developmental age at exposure, and also appear specific for Ca2+-dependent ATPase activity. Furthermore, THC exposure modulates pituitary sensitivity to LHRH receptor-mediated effects on Ca2+ ATPase activity. Therefore, effects on Ca2+ membrane transport may be involved in acute THC actions on hormonal activity at these HPG sites.

Animals↗

PubMed1987

LHRH-receptor-regulated Ca2+-ATPase activity in murine pituitary gland.

Addition of luteinizing hormone releasing hormone (LHRH) in vitro (10(-5) -5 X 10(-9) M) to murine pituitary membranes resulted in a dose-related decrease in Ca2+-ATPase activity within 15 min. Inhibitory effects of LHRH (10(-7) M) occurred after 90 sec, and appeared maximal by 120 sec. Eadie-Hofstee analysis at 10(-7) M LHRH, at varying [Ca2+]free, resulted in a Km = 0.89 +/- 0.06 microM and a Vmax = 18.8 +/- 0.71 nmol/mg per 2 min, compared to a Km = 0.69 +/- 0.06 microM and a Vmax = 32.8 +/- 1.21 nmol/mg per 2 min for controls. Pre-incubation for 5 min with LHRH antagonist (10(-8) M) significantly attenuated (50%) the inhibitory effects of 10(-7) M LHRH on pituitary Ca2+ ATPase activity with a Km = 0.97 +/- 0.24 microM and a Vmax = 28.1 +/- 2.8 nmol/mg per 2 min. The addition of LHRH (10(-7) M) to pituitary homogenates significantly increased luteinizing hormone (LH) release already at 10 and up to 40 sec compared to basal LH release. Systemic administration of 50 ng LHRH (i.p.), significantly (P less than 0.05) reduced pituitary Ca2+-ATPase after 30, 60 and 90 min, with a return to control levels by 120 min. Pituitary LH content was reduced slightly at 15 min, but was increased significantly at 90 and 120 min post-treatment. Plasma LH levels were elevated by 5 min, reached a peak by 15 min and returned to control within 60 min. The present findings indicate that LHRH receptor activation may influence cytosolic Ca2+ transport through effects on membrane Ca2+-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Differential effects of follicle-stimulating and luteinizing hormones on testosterone production by mouse testes.

In adult mice, direct intratesticular injection of ovine follicle-stimulating hormone (o-FSH-13; AFP 2846-C, from NIAMDD, less than 1% LH contamination) at 10, 100 or 1000 ng significantly elevated concentrations of testosterone (T) within the testis. These effects were rapid, with peak values attained by 15 min, and transient, with return to values comparable to that in the contralateral, saline-injected testis within 90 min. Intratesticular injection of FSH (1 microgram) significantly increased testicular T levels in 15- and 60-day old mice. This contrasted with the effects of intratesticular administration of human chorionic gonadotropin (hCG), which stimulated T production significantly at 30 days of age through adulthood. In adult mice, the equivalent LH to the possible contamination in the FSH preparation (1 ng) had no effect. Intratesticular injection of 10 ng LH produced comparable stimulation to that by 100 ng FSH (approximately 7-fold). Systemic pre-treatment with a charcoal-treated porcine follicular fluid (PFF) extract for 2 days reduced plasma FSH levels [86 +/- 17 (5) vs 700 +/- 8 (6); P less than 0.05], but had no effect on plasma LH. Twenty-four hours after the last treatment, the response to intratesticular injection of hCG (2.5 mIU), FSH (100 ng) or LH (10 ng) was also significantly attenuated in these mice. Intratesticular injection of PFF had no direct effect on testicular T levels. In vitro T production in the presence of hCG, LH or FSH were differentially affected by the concentrations of calcium (Ca2+) or magnesium (Mg2+) in the incubation media. The stimulatory effects of FSH were apparent at significantly lower levels of Ca2+ or Mg2+, than were those of LH or hCG. The results of these studies indicate that FSH is capable of stimulating testicular T production. Furthermore, the responsiveness to FSH is qualitatively different than that to LH/hCG in terms of the age pattern, as well as the dependence on Ca2+ or Mg2+. In addition, plasma FSH levels appear to influence testicular responsiveness to direct exogenous administration of gonadotropins. These studies indicate that FSH stimulation of T production can be differentiated from those of LH, and that these effects of FSH can be observed under physiological conditions.

Age Factors↗

PubMed1986

Maternal cannabinoid exposure. Effects on spermatogenesis in male offspring.

Maternal exposure to cannabinoids influenced spermatogenesis and fertility in their male offspring examined at 60-80 days of age. Approximately 20% less spermatozoa were found in males whose mothers had received either the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) on day 1 postpartum. Males exposed to the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (THC) appeared to have spermatozoa in number comparable to controls. This finding may be consistent with the additional observation that CBN or CBD, but not THC, reduced the percentage of successful impregnations by cannabinoid-exposed males. However, males exposed to each of these cannabinoids produced significantly less live offspring compared to controls. Plasma levels of testosterone and luteinizing hormone (LH) were reduced significantly in mice exposed to THC on day 12 of gestation, while testicular weight was reduced in adult mice exposed either on day 12 of gestation to CBD or on day 1 post-partum to THC. These results indicate that perinatal exposure to psychoactive and non-psychoactive components of marihuana can produce long-term disruption of testicular function including the spermatogenic as well as the steroidogenic components.

Animals↗

PubMed1979

Role of the pituitary and the adrenals in mediating the effects of alcohol on testicular steroidogenesis in mice.

We have previously demonstrated that intragastric administration of alcohol (1.24 g/kg body wt) to adult male mice results in suppression of testosterone production. We now report that the decline in peripheral testosterone levels in alcohol-treated mice is not accompanied by changes in plasma levels of luteinizing hormone, follicle stimulating hormone or estradiol-17 beta, and that it is markedly attenuated in adrenalectomized or adrenalectomized-corticosterone treated males.

Adrenal Glands↗

PubMedDate not supplied

Ethanol-diazepam interactions on delayed match-to-sample performance in baboons.

Four juvenile male baboons were trained on a delayed match-to-sample (MTS) discrimination task. Single administration of 0.25, 0.5, 1.0, 2.0, 4.0, and 6.0 mg/kg diazepam (DZ) resulted in a dose-related increase in mean response time (MRT), with a maximum effect at 2.0 mg/kg. Administration of 0.25 mg/kg of DZ had no effect. Response time was increased significantly by 1.0 g/kg of ethanol (EtOH) but was not affected by 0.5 g/kg EtOH. There were no significant effects on the number of correct responses. Combined treatment of 0.5 g/kg of EtOH with 1.0 mg/kg DZ produced the same increase in MRT as the DZ alone. When 1.0 g/kg EtOH was administered with 0.25 mg/kg DZ. MRT decreased which was a significant improvement in performance as compared to the increase in MRT observed with either the EtOH or the DZ alone. Combined doses of 1.0 g/kg EtOH and 0.5 mg/kg DZ produced essentially the same increases in MRT as either dose alone. Similar results were obtained when 1.0 g/kg EtOH and 1.0 mg/kg DZ were combined and the increase in MRT was about the same for DZ alone and more than twice as great for the EtOH alone. Combined administration of the drugs had no significant effects on the number of correct choices. Since the administration of a combination of a low dose of DZ with EtOH appeared to prevent the increases in MRT observed with either drug alone and there were no observable effects on the number of correct response, these effects do not appear to involve cognitive processes but might be related to excitability changes in motor systems.

Animals↗

PubMedDate not supplied

Ethanol and diazepam interactions on conflict behavior in rats.

Twenty-four adult male rats trained on the Geller-Seifter conflict procedure received: 1.0, 2.0, or 4.0 mg/kg diazepam at 15 min, 0.25, 0.5, 1.0, 2.0, or 4.0 g/kg of ethanol (EtOH) at 30 min prior to the test session, or combinations of the same diazepam doses and 0.5 g/kg of EtOH. Ethanol administration produced a significant (p less than 0.05) dose-related decrease in lever pressing during the periods prior to the introduction of the tone stimulus, compared to lever pressing during the corresponding control periods on the day prior to drug treatment. During the posttone periods 0.25 g/kg increased lever pressing (p less than 0.05), while doses of EtOH from 0.5 to 4.0 g/kg resulted in significantly lower levels of lever pressing in periods following the discontinuation of the tone. In the presence of the conflict evoking tone stimulus, rats treated with 2.0 g/kg of EtOH increased their rate of lever pressing, while animals receiving the other EtOH doses exhibited lever pressing comparable to that observed during the corresponding control periods. Administration of EtOH had no effect on the number of reinforcements received during the entire test session, except for a significant (p less than 0.05) reduction at the highest dose of 4.0 g/kg. Diazepam increased the number of reinforcements received during the entire test session as compared to those obtained during control sessions. Lever pressing was not affected by diazepam treatment during pretone or tone periods. During the posttone periods responses were significantly (p less than 0.05) increased in rats receiving the lowest dose of 1.0 mg/kg of diazepam but the other doses were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Interactive effects of diazepam and ethanol on baboon match-to-sample performance.

Four juvenile male baboons were trained to perform a match-to-sample (MTS) discrimination task. Diazepam (DZ) at doses of 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg resulted in a significant (p less than 0.05) increase in the mean response times (MRT) during the 2 hr test session in terms of percent change from baseline performance under nondrug conditions measured the day prior to drug treatment. Effects were maximal at 2.0 mg/kg diazepam and no further effects were observed at 4.0 or 6.0 mg/kg. Administration of 0.25 mg/kg of diazepam had no effect on MTS performance. Exposure to 0.5 g/kg of ethanol (EtOH) had no effect on response time, while 1.0 g/kg EtOH significantly (p less than 0.05) increased response time. Baboons receiving combined treatment with 0.5 or 1.0 g/kg EtOH plus 1.0 mg/kg diazepam displayed a significant (p less than 0.05) percent increase in mean response time compared to that observed under baseline conditions on the day prior to drug treatment. The 0.5 g/kg EtOH and 1.0 mg/kg diazepam combination increased MRT to an extent comparable to the effect observed at the same dose of diazepam alone. Effects observed with 1.0 mg/kg diazepam and 1.0 g/kg EtOH were similar to those produced by the DZ alone. Combinations of 0.5 g/kg EtOH and 0.5 mg/kg diazepam, 1.0 g/kg EtOH and 0.25 mg/kg diazepam, and 1.0 g/kg EtOH and 0.5 mg/kg diazepam had no significant effect on response times.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Ethanol and chronic diazepam interactions on conflict behavior in rats.

Four groups of five rats each received training on the Geller-Seifter procedure and then received 0.5, 1.0 or 2.0 mg/kg diazepam (DZ) or vehicle, respectively, 15 min prior to the behavior sessions for 14 days. On Day 14 of DZ treatment rats also were administered 2.0 g/kg of ethanol (EtOH) 30 min prior to testing. Significant dose-related decreases in lever pressing occurred between groups over the 13 days of DZ treatment during the pre- and posttone periods. However, a significant effect attributable to days occurred only in the pretone period. During the tone period, the dose-related effects were greater but the variability also increased and specific contrasts between individual means were not significant. The largest increases in lever pressing associated with an anxiolytic effect occurred with 1.0 mg/kg of DZ at Day 6. On Day 14, all animals received 2.0 g/kg of EtOH and their performance was compared to performance on Day 13. During the pre- and posttone periods, the EtOH resulted in significantly less lever pressing in the control, 0.5 and 2.0 mg/kg DZ groups, indicating a sedative effect. Rats treated with 1.0 mg/kg of DZ did not exhibit this EtOH reduction in lever pressing. During the tone or conflict period, a significant dose-related increase in lever pressing due to the EtOH was observed. The increase in the control group was not significant. During repeated exposure to DZ there was a small but significant decrease in number of reinforcements which was enhanced by the EtOH at the 0.5 and 2.0 mg/kg DZ doses but not at 1.0 mg/kg DZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Cannabinoid exposure: effects on development.

The literature concerning the teratologic effects of cannabinoids is reviewed, and some methodological issues associated with perinatal cannabinoid exposure are discussed. The long-term consequences of perinatal cannabinoid exposure on brain, endocrine, immune, and hepatic functions are considered. In our studies, perinatal cannabinoid exposure affected the long-term development of body weight regulation, neuroendocrine function, and adult sexual behaviors. In addition, the immune system and hepatic cytochrome P-450 levels were also influenced in adult male mice perinatally-exposed to cannabinoids. It is hypothesized that these effects may be mediated by cannabinoid-induced alterations in the fetal and/or neonatal hormonal milieu. In addition, the possibility that perinatal cannabinoid administration affects the subsequent ability of the exposed offspring to adapt to the environment is discussed. Finally, possible mechanisms of cannabinoid action in altering development are evaluated. It is concluded that the evidence to date indicates that cannabinoids can be embryocidal, affect gestational length and labor, induce maturational delays, and that these substances affect a myriad of physiological processes in the developing offspring, including effects on behavioral parameters, not only in laboratory animals, but also in the human neonate. Consequences of perinatal cannabinoid exposure on development are described and possible mechanisms of action of cannabinoids are discussed.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Perinatal cannabinoid exposure: demasculinization in male mice.

Maternal exposure to psychoactive or non-psychoactive cannabinoids produces long-term changes in body weight regulation, pituitary-gonadal feedback, testicular function, and also affects adult sexual behavior in male offspring. Alterations in brain biogenic amine concentration and metabolism have also been observed in adult males perinatally-exposed to cannabinoids. The possibility that these effects are mediated by cannabinoid-induced suppression or interference with fetal and/or neonatal androgen production is discussed. In addition, data are presented showing that exposure to the major psychoactive component of marihuana, delta 9-tetrahydrocannabinol (THC), on day 12 of gestation significantly increased hepatic cytochromes P-450 levels. In contrast, cytochromes P-450 levels were significantly decreased in adult males exposed to these cannabinoids on day 1 post-partum. The response of these animals to the negative feedback effects of exogenous androgen was also influenced by perinatal cannabinoid exposure. One hr after injection of 20 micrograms testosterone (T), plasma levels of luteinizing hormone (LH), were markedly increased in castrated males exposed to CBD on day 12 of gestation, while the THC and control mice showed no response to T injection. In contrast to the reduced plasma LH levels in the controls, the levels of LH were significantly increased in postnatal THC-exposed males, while the CBN and CBD-exposed mice exhibited no reduction in plasma LH in response to exogenous androgen. Prenatal exposure to THC resulted in a greater suppression of plasma follicle-stimulating hormone (FSH) levels in mice receiving 20 micrograms T, compared to the effects in the castrated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗