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Biomedical subjects

R N Pechnick

Publications and source records attributed to R N Pechnick.

At least 37 records · Page 2Linked to original sources
PubMed1989

Comparison of the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat.

Some of the dioxolanes produce pharmacological effects that have much in common with phencyclidine and phencyclidine-like drugs. Dioxadrol can be resolved into two enantiomers, dexoxadrol and levoxadrol. Dexoxadrol has an affinity for phencyclidine receptors that is much greater than that of levoxadrol, but dexoxadrol and levoxadrol have nearly equal affinities for sigma receptors. The systematic analysis of the relative potencies of dexoxadrol and levoxadrol can be used as an approach to define effects mediated by phencyclidine vs sigma receptors. Compounds that act on phencyclidine receptors, as well as affecting behavior, alter body temperature in the rat. The purpose of the present study was to compare and contrast the effects of the acute administration of dexoxadrol, levoxadrol, MK-801 and phencyclidine on body temperature in the rat. Dexoxadrol and levoxadrol (5.0, 10.0, 20.0 or 40.0 mg/kg), MK-801 (0.12, 0.6 or 1.2 mg/kg) or phencyclidine (5.0, 10.0 or 20.0 mg/kg) were administered subcutaneously and body temperature was measured. Both dexoxadrol and MK-801 produced hyperthermia but levoxadrol did not affect body temperature. In contrast to the hyperthermic effects of dexoxadrol and MK-801, phencyclidine produced hypothermia. These findings indicate that hypothermia induced by phencyclidine is not due to interactions with phencyclidine receptors and, while dexoxadrol, MK-801 and phencyclidine may share some similar receptor binding and behavioral characteristics, they can be differentiated on the basis of their effects on body temperature.

Animals↗
PubMed1989

Characterization of the effects of the acute and chronic administration of phencyclidine on body temperature in the rat: lack of evidence for the involvement of opiate receptors.

The present study characterized the effects of the acute and chronic administration of phencyclidine on body temperature in the rat. The acute administration of phencyclidine produced hypothermia. This hypothermia occurred only after high doses of drug. In contrast, only hyperthermia was found in chronically treated subjects. The hyperthermia in chronically treated subjects was produced by low doses of drug, and sensitization to the hyperthermic effects took place over time. There was no evidence for the involvement of opiate receptors in the acute hypothermic response to phencyclidine, as the hypothermia was not antagonized by naloxone or decreased in chronically morphine-treated subjects. Moreover, the hypothermic response was enhanced by treatment with opiate receptor-active and -inactive enantiomers of naloxone, as well as in chronically morphine-treated subjects.

Animals↗
PubMed1989

Characterization of the effects of the acute and chronic administration of phencyclidine on the release of adrenocorticotropin, corticosterone and prolactin in the rat: evidence for the differential development of tolerance.

Phencyclidine (PCP) is a widely used drug of abuse; however, little is known of its effects on neuroendocrine function. The present study characterized the effects of the acute and chronic administration of PCP on the release of adrenocorticotropin, corticosterone and prolactin in the rat. For the acute studies, PCP hydrochloride (0.5-10.0 mg/kg s.c.) was administered and the subjects were sacrificed 15 to 300 min later. The acute administration of PCP produced rapid and long-lasting increases in plasma levels of adrenocorticotropin and corticosterone but decreased plasma levels of prolactin. For the chronic studies, PCP (1.0-20.0 mg/kg/day s.c.) was injected daily and the subjects sacrificed 60 min after injection on day 15. PCP continued to stimulate the pituitary-adrenal axis after chronic administration; however, there was a decrease in the magnitude of response, indicating the development of some degree of tolerance. In contrast, none of the doses of PCP tested decreased plasma prolactin levels in chronically treated subjects. There were no differences in plasma or brain levels of PCP in the chronically PCP-treated rats, indicating that tolerance was not due to changes in the biodisposition of PCP. These results indicate that PCP disrupts neuroendocrine function markedly in the rat. The differential development of tolerance to the effects of PCP on the pituitary-adrenal axis and prolactin release may indicate that different neurochemical substrates underlie the effects of PCP on different endocrine systems.

Adrenocorticotropic Hormone↗
PubMed1989

Pharmacokinetic and pharmacodynamic evaluation of phencyclidine and its decadeutero variant.

The role of metabolism in the in vivo actions of phencyclidine (PCP) was examined by comparing deuterium-substituted drug with drug of normal isotopic abundance. PCP elicits two responses that differ in their time course, ataxia, which is observable immediately after dosage, and hypothermia, which peaks approximately 90 to 120 min after drug administration. The role of metabolism in these responses was determined by comparing bioavailabilities of deuterium enriched (d10) and normal (d0) PCP with the two responses. Plasma concentration was determined after the i.v. and i.p. administration of d10 and d0 drug and the bioavailability of the d10 was found to be 1.3 to 1.5 times the d0. The clearance of the d10 was also smaller than the d0. The d10, which is pharmacologically equivalent in vitro, is metabolized more slowly than the d0 in vitro. The pharmacokinetic and pharmacodynamic bioavailabilities exhibited comparable isotope effects, indicating that both responses are due to the actions of the parent drug.

Animals↗
PubMed1988

Relationship between analgesia and cardiovascular changes induced by electrical stimulation of the mesencephalic periaqueductal gray matter in the rat.

Analgesia and cardiovascular changes produced by electrical stimulation of the midbrain periaqueductal gray matter were examined in the lightly pentobarbital-anesthetized rat. The current intensity required to elicit analgesia was first determined, using the tail-flick test, after which the effects on arterial pressure and heart rate were recorded from stimulating at the same intensity. Intensity thresholds for decreases and/or increases in arterial pressure were also ascertained at the same sites. Although stimulation at the analgesia threshold produced increases in arterial pressure at more than 60% of the sites within the periaqueductal gray, decreases, no change, and mixed responses were also observed. Below the periaqueductal gray, increases in arterial pressure occurred at analgesia threshold for more than 70% of the sites studied, and no cardiovascular changes were found for 20% of the sites. Above the periaqueductal gray, no change and mixed responses were the predominant effects at analgesia threshold. A correlation across sites within the periaqueductal gray was found between the threshold for stimulation-produced analgesia and the threshold for a change in arterial pressure. No reliable alterations in heart rate were observed at any stimulation site. These results are in agreement with the existence of a common midbrain substrate for both the regulation of pain inhibition and cardiovascular function. However, they indicate that analgesia resulting from stimulation of the periaqueductal gray matter does not necessarily occur concurrently with an increase in arterial pressure.

Analgesia↗
PubMed1987

The role of opiate receptors in the potentiation of pentobarbital sleeping time by the acute and chronic administration of opiates.

Male rats injected with pentobarbital (50.0 mg/kg i.p.) showed increased sleeping time after the acute administration of morphine (5.0 or 10.0 mg/kg s.c.). This effect was antagonized by naltrexone (2.0 mg/kg s.c.). The enhancement displayed stereoselectivity as levorphanol greatly lengthened the sleeping time induced by pentobarbital while dextrophan only produced a slight increase. Rats implanted for 3 days with pellets of morphine base (75.0 mg) were tolerant to the analgesic effects of morphine (2.5 mg/kg s.c.) but showed an even greater increase in pentobarbital-induced sleeping time than rats treated acutely. No potentiation was observed in subjects that were also implanted with a pellet of naltrexone (30.0 mg). It is concluded that the potentiation of pentobarbital-induced sleeping time produced by opiates is mediated by opiate receptors, but fails to show the development of tolerance.

Animals↗
PubMed1987

The role of endogenous opioids in footshock-induced hyperthermia.

Either opioid or nonopioid forms of stress-induced analgesia can be elicited depending on the intensity or duration of the stressor. Several forms of stress have also been shown to cause hyperthermia in the rat. The present study investigated whether opioid and nonopioid forms of such stress-induced hyperthermia can be elicited in the rat as a function of footshock current intensity. Rats were given footshock after pretreatment with saline or naltrexone, or chronic morphinization. Footshock produced hyperthermia, the degree of which was found to be a function of current intensity. While the peak rise in temperature was not affected by naltrexone or chronic morphine administration, the rate of return to baseline temperature was slowed by these treatments. Thus, the endogenous opioid system appears to be involved in the return to normal body temperature following footshock, but not in the footshock-induced rise in temperature.

Animals↗
PubMed1987

The effects of the systemic administration of N-methylmorphine chloride, a quaternary analogue of morphine that does not cross the blood-brain barrier, on the release of anterior pituitary hormones in the rat.

The acute administration of morphine elicits changes in the release of anterior pituitary hormones. The locus of this action is thought to be in the central nervous system, specifically the hypothalamus. There are some data suggesting that systemically administered opiates and opioid peptides can act outside of the blood-brain barrier to influence anterior pituitary hormone release. To test this hypothesis we examined the effects of the systemic administration of N-methylmorphine chloride, a quaternary analogue of morphine that does not cross the blood-brain barrier, on the release of corticosterone, growth hormone, prolactin, luteinizing hormone, and thyroid stimulating hormone in the rat. N-methylmorphine caused increases in the release of growth hormone and prolactin, but serum levels of corticosterone, luteinizing hormone and thyroid stimulating hormone were unaffected. These results indicate that the opiate-induced release of growth hormone and prolactin may be mediated in part by sites outside of the blood-brain barrier.

Adrenocorticotropic Hormone↗
PubMed1986

The effects of the acute administration of phencyclidine hydrochloride (PCP) on the release of corticosterone, growth hormone and prolactin in the rat.

There is little information on the neuroendocrine effects of PCP. The present study examined the effects of the acute subcutaneous administration of PCP on serum levels of corticosterone, growth hormone and prolactin in the male rat. PCP increased serum levels of corticosterone, decreased serum levels of prolactin and failed to affect growth hormone levels. The results indicate that, like other drugs of abuse, PCP alters neuroendocrine function.

Animals↗
PubMed1986

Involvement of brain opiate receptors in the immune-suppressive effect of morphine.

We previously reported that a single systemic injection of a high dose of morphine (greater than or equal to 20 mg/kg) transiently suppresses splenic natural killer cell cytotoxicity in rats. The present study examined the possibility that the immune-suppressive effect of morphine is mediated by opiate receptors in the brain. Supporting this hypothesis, we found that morphine (20 or 40 micrograms) injected into the lateral ventricle suppressed natural killer cell activity to the same degree as a systemic dose higher by three orders of magnitude. This effect was blocked by an opiate antagonist, naltrexone. Natural killer cell activity was unaffected by systemic administration of N-methyl morphine, a morphine analogue that does not cross the blood-brain barrier. These data implicate opiate receptors in the brain in morphine-induced suppression of natural killer cell cytotoxicity.

Animals↗
PubMed1985

The effects of the acute administration of buprenorphine hydrochloride on the release of anterior pituitary hormones in the rat: evidence for the involvement of multiple opiate receptors.

Multiple opiate receptor agonists and antagonists have been found to produce different patterns of anterior pituitary hormone release. The present studies examined the pattern of anterior pituitary hormone release produced by buprenorphine. The effects of the kappa agonist ethylketocyclazocine on thyroid stimulating hormone release were also examined. Following buprenorphine, serum levels of corticosterone and luteinizing hormone were not changed while growth hormone release was stimulated in a dose-dependent manner. Prolactin release was stimulated after the lowest dose of buprenorphine while the highest dose induced a fall in serum prolactin. Similar biphasic effects on thyroid stimulating hormone were seen after either buprenorphine or ethylketocyclazocine. The results provide support for the role of multiple opiate receptors in opiate-induced changes in anterior pituitary hormone release.

Animals↗