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R N Pechnick

Publications and source records attributed to R N Pechnick.

At least 19 recordsLinked to original sources
PubMed2000

Comparison of noncontingent versus contingent cocaine administration on plasma corticosterone levels in rats.

The purpose of the present study was to compare the effects of contingent and noncontingent cocaine administration on plasma levels of corticosterone in rats. Male rats were trained to self-administer cocaine under a fixed-ratio 5 schedule. The rats were yoked such that the delivery of cocaine (0.25 mg/kg/infusion) to one rat (contingent cocaine) produced the simultaneous noncontingent delivery of the same dose of cocaine (noncontingent cocaine) or saline (noncontingent saline) to other rats. Although saline administration had no effect, plasma corticosterone levels were significantly higher in rat receiving contingent cocaine compared to those receiving noncontingent cocaine. These results demonstrate that the active vs. passive administration of cocaine can differentially affect this neuroendocrine response.

Analysis of Variance↗
PubMed2000

Effect of cigarette smoking on coumarin metabolism in humans.

Extant data, mostly from studies in vitro, suggest that coumarin and nicotine are both metabolized by CYP2A6, a cytochrome P450 isozyme. In order to investigate this issue further, the activity of this enzyme in vivo was measured in 37 non-smokers and 37 smokers using coumarin (2.0 mg, PO) as the metabolic probe. The percentage of coumarin metabolized to 7-hydroxycoumarin in 8 h was measured in urine by high-pressure liquid chromatography. There was more than 10-fold variability in coumarin metabolism in both groups. Coumarin metabolism was significantly reduced in smokers (46.6 +/- 4.4%) as compared to non-smokers (66.4 +/- 3.5%; p < or = .001). The results support previous in vitro findings that both coumarin and nicotine are metabolized, at least in part, by a common pathway, which most likely is CYP2A6.

Administration, Oral↗
PubMed1997

Abnormal ACTH and prolactin responses to fenfluramine in rats exposed to single and multiple doses of MDMA.

The present study examined the persistent functional consequences associated with exposure to single and multiple doses of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) as reflected by the neuroendocrine responses to d,l-fenfluramine (FEN). Adult male rats were administered a single dose of MDMA (20 mg/kg, s.c.) and challenged 2 weeks later with saline or FEN (2, 4, 6 and 8 mg/kg, s.c.). The corticotropin (ACTH) response to FEN (6 and 8 mg/kg) was blunted and the prolactin response to FEN (4 and 6 mg/kg) was enhanced in MDMA pre-treated rats. The ACTH and prolactin responses to FEN (6 mg/kg, s.c.) were then evaluated 4, 8 and 12 months after exposure to single and multiple doses MDMA (20 mg/kg, s.c. and 20 mg/kg, s.c., bid, x 4 days, respectively). The ACTH response to FEN was significantly reduced at 4 and 8 months in both MDMA treatment groups, and at 12 months in the multiple dose group only. In contrast, the prolactin response to FEN was enhanced in both groups of MDMA treated rats at 4 months, but only in the multiple dose group at 8 months. By 12 months, the prolactin response to FEN had normalized. Following multiple doses of MDMA, 5-HT concentrations were reduced significantly in the frontal cortex at 4 and 12 months. The results indicate that exposure to single or multiple doses of MDMA can produce functional alterations which can persist for months, whereas the biochemical sequelae were less robust and shorter lived.

Adrenocorticotropic Hormone↗
PubMed1995

Antinociception following 1,3,-di-o-tolylguanidine, a selective sigma receptor ligand.

The role of sigma receptors in antinociceptive processes remains equivocal, because previous sigma drugs also bind to PCP/NMDA and opiate receptors. The present study examined the antinociceptive effects of the high-affinity, sigma-selective ligand 1,3-di-o-tolylguanidine (DTG; 10, 15, and 20 mg/kg, IP) on tail-withdrawal latencies in mice. DTG produced significant but short-lived increases in withdrawal latencies at all dose levels. DTG also produced hypothermia, but this effect was dissociable from antinociception. The highly selective sigma ligand rimcazole (10 and 25 mg/kg, IP) antagonized DTG antinociception in a dose-dependent manner. The opiate antagonist naloxone and the PCP/NMDA antagonist MK-801 were, however, without effect. Haloperidol, which also binds to sigma receptors, increased withdrawal latencies but did not alter DTG antinociception. These data implicate sigma receptors as the site of DTG antinociception, and more generally support the distinction between sigma, opiate, and PCP/NMDA receptors.

Analysis of Variance↗
PubMed1995

1,3-Di-o-tolylguanidine (DTG) differentially affects acute and tonic formalin pain: antagonism by rimcazole.

The role of the sigma receptor in prolonged pain was examined by assessing the effects of 1,3,di-o-tolylguanidine (DTG), a selective sigma receptor ligand, on the formalin test in mice. Formalin injected subcutaneously into the hindpaw produces a biphasic pain response: an acute phase of short duration followed by a longer-lasting tonic phase. DTG (10 mg/kg, i.p.) potently reduced pain behavior in the acute phase but increased pain behavior in the tonic phase. Rimcazole (5 and 10 mg/kg, i.p.), a selective sigma receptor antagonist, blocked both the DTG-induced decrease and increase in pain behavior observed in the acute and tonic phases, respectively. These data support previous findings indicating a modulatory role for the sigma receptor in nociceptive processes, and suggest that this receptor differentially modulates acute vs. tonic pain.

Animals↗
PubMed1994

Neuroendocrine responses produced by enantiomeric pairs of drugs that interact with phencyclidine and sigma receptors.

The present study characterized the response of the hypothalamo-pituitary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)-pentazocine produced greater responses than (+)-pentazocine, the two enantiomers of SKF 10,047 did not show stereoselectivity. Although the potency of the enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP receptors, the potency of the enantiomers of pentazocine did not. These results suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis by PCP and drugs with PCP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.

Adrenocorticotropic Hormone↗
PubMed1994

The effects of MK-801 on body temperature and behavior in the rat: cross-sensitization and cross-tolerance with phencyclidine.

The purpose of the present study was to compare the acute and repeated administration of MK-801 (dizocilpine) on body temperature and behavior in the rat, and to determine whether there is cross-tolerance and/or cross-sensitization to phencyclidine (PCP) after repeated administration of MK-801. The acute administration of MK-801 increased body temperature, and this response was enhanced after repeated drug administration. PCP had little effect on body temperature in control rats, but produced increases in body temperature in rats treated daily with MK-801. The acute administration of MK-801 produced ataxia, locomotion, sniffing, and head-weaving, and after repeated drug administration both ataxia and head-weaving were reduced. PCP-induced ataxia, backpedalling, head-weaving, and turning behaviors were decreased in rats treated daily with MK-801, but PCP-induced locomotion and rearing were increased. These results indicate that there is cross-sensitization to the hyperthermic and locomotor effects of MK-801 and PCP, but there is cross-tolerance to some of the other behavioral effects of the drugs.

Animals↗
PubMed1991

Effects of subcutaneous and intracerebroventricular administration of the sigma receptor ligand 1,3-Di-o-tolylguanidine on body temperature in the rat: interactions with BMY 14802 and rimcazole.

The current study investigated the effects of the acute s.c. and i.c.v. administration of 1,3-di-o-tolylguanidine (DTG) on body temperature in rats. The effects of putative sigma receptor antagonists BMY 14802 and rimcazole on DTG-induced changes in body temperature also were evaluated. The acute s.c. administration of DTG (10.0 and 20.0 mg/kg) produced hypothermia but no observable behavioral effects. Similarly, the acute i.c.v. administration of DTG (12.0-100.0 micrograms/rat) produced hypothermia, but ataxia occurred after this route of administration. The s.c. administration of BMY 14802 alone (25.0 mg/kg) decreased body temperature and enhanced the DTG-induced hypothermia, whereas the administration of rimcazole (25.0 mg/kg) neither altered body temperature nor affected the hypothermia produced by DTG. Neither BMY 14802 nor rimcazole produced any behavioral effects when administered alone. The inability of the putative sigma receptor antagonists BMY 14802 and rimcazole to antagonize DTG-induced hypothermia suggests that either these compounds at the dose used have little sigma receptor antagonist activity, or that the DTG-induced hypothermia is not due to specific interactions with sigma receptors.

Animals↗
PubMed1991

Binding affinity and antimuscarinic activity of sigma and phencyclidine receptor ligands.

The characterization of the sigma receptor has been hampered by the lack of a functional bioassay system. Drugs that bind to sigma receptors have been reported to inhibit carbachol-induced phosphatidylinositol turnover in rat brain; however, these drugs might directly affect muscarinic acetylcholine receptors. The purpose of the present study was to determine the affinity for muscarinic receptors and the antimuscarinic activity of sigma and phencyclidine receptor ligands. All of the drugs tested inhibited the binding of [3H]N-methylscopolamine to guinea pig cerebral cortical membranes with KI values in the micromolar range and also inhibited carbachol-induced contractions in the guinea pig ileum. These results demonstrate that these compounds have substantial antimuscarinic activity which might limit the use of the inhibition of carbachol-induced phosphatidylinositol turnover as a functional assay system for studying sigma ligands. Furthermore, this antimuscarinic activity must be considered when evaluating the effects of these compounds after in vivo administration.

Animals↗
PubMed1990

Effects of acute and chronic administration of (+)-SKF 10,047 on body temperature in the rat: cross-sensitization with phencyclidine.

The current study investigated the effects of acute and chronic administration of (+)-SKF 10,047 on body temperature in rats. The effect of phencyclidine on body temperature in chronically (+)-SKF 10,047-treated rats was also investigated. The acute administration of (+)-SKF 10,047 at doses of 5 to 40 mg/kg s.c. did not alter body temperature; however, 80 mg/kg produced hypothermia. In contrast, chronic administration of (+)-SKF 10,047 (5-20 mg/kg) produced dose-dependent hyperthermia when tested on day 7 and 10 of chronic treatment. Moreover, sensitization to the hyperthermic effects occurred as the degree of hyperthermia was greater on day 10 compared to day 7. Phencyclidine (20 mg/kg s.c.) produced hypothermia in rats chronically treated with saline for 13 days, but hyperthermia in rats chronically treated with 20 mg/kg of (+)-SKF 10,047 for the same duration. The hyperthermic effect of chronic (+)-SKF 10,047 treatment is similar to the previously reported dose-dependent hyperthermia in chronically phencyclidine-treated animals. The cross-sensitization of chronically (+)-SKF 10,047-treated rats to the hyperthermic effects of phencyclidine supports the hypothesis that there may be common mechanisms underlying the chronic effects of these drugs on body temperature.

Animals↗
PubMed1990

Determination of the loci of action of phencyclidine on the CNS-pituitary-adrenal axis.

Phencyclidine (PCP) markedly stimulates the pituitary-adrenal axis in the rat, inducing the release of adrenocorticotropin (ACTH) and corticosterone. However, the site or sites where PCP produces these effects is not known. This study sequentially examined the effects of PCP on the different components of the central nervous system-pituitary-adrenal axis. PCP did not produce corticosterone release in dispersed adrenal cells in vitro, nor did it stimulate the release of corticosterone in hypophysectomized rats, showing that PCP-induced corticosterone release in intact animals is secondary to the release of ACTH from the pituitary. PCP failed to alter either the basal or the corticotropin releasing factor-induced release of ACTH from superfused pituitaries in vitro, indicating that PCP does not act directly at the level of the pituitary. PCP increased plasma levels of ACTH in adrenalectomized rats, demonstrating that PCP does not stimulate the release of ACTH only by blocking glucocorticoid negative feedback mechanisms. PCP stimulated the release of both ACTH and corticosterone when given by injection directly into brain via the lateral cerebral ventricles. These results indicate that PCP activates the pituitary-adrenal axis by acting at a site or sites within the central nervous system, leading to the subsequent release of ACTH from the pituitary.

Adrenocorticotropic Hormone↗
PubMed1989

Naloxone does not produce withdrawal hypothermia in chronically phencyclidine-treated rats.

Naloxone-induced hypothermia is a sensitive indicator of mu-type opiate dependence in the rat. The present study investigated whether naloxone produces hypothermia in chronically PCP-treated rats. Rats were given daily injections of saline or PCP (10.0 mg/kg s.c.) for 7 days, and on day 8 challenged with naloxone (2.0 mg/kg s.c.). There were no differences between chronic saline- and PCP-treated subjects, indicating that the repeated administration of 10.0 mg/kg per day of PCP does not produce mu-type opiate dependence as reflected by naloxone-precipitated hypothermia.

Animals↗
PubMed1989

Characterization of the effects of the acute and repeated administration of MK-801 on the release of adrenocorticotropin, corticosterone and prolactin in the rat.

In addition to its producing profound changes in behavior, phencyclidine (PCP) disrupts neuroendocrine function in the rat. Because PCP binds to PCP as well as sigma receptors, it is not known which receptor type mediates the various effects of the drug. The purpose of the present study was to characterize the effects of the acute administration of enantiomers of MK-801, a compound with a high degree of selectivity for PCP over sigma receptors, on the release of ACTH, corticosterone and prolactin in the rat. In addition, MK-801 was administered daily for eight days in order to test whether tolerance develops to MK-801-induced ACTH and corticosterone release after repeated administration. While both enantiomers of MK-801 markedly increased plasma levels of ACTH and corticosterone, the (+) enantiomer was more potent. Tolerance developed to MK-801-induced increases in ACTH and corticosterone after repeated administration. Plasma prolactin levels were not affected by either the acute or the repeated administration of MK-801. These results suggest that the decrease in plasma levels of prolactin produced by PCP-like drugs is not mediated by PCP receptors, and may be a marker for a sigma receptor-mediated effect.

Adrenocorticotropic Hormone↗
PubMed1989

Naloxone does not antagonize PCP-induced stimulation of the pituitary-adrenal axis in the rat.

Phencyclidine (PCP) has been shown to stimulate the pituitary-adrenal axis in the rat. The purpose of the present study was to determine whether opiate receptors are involved in this effect by testing whether pretreatment with the opiate antagonist naloxone can antagonize PCP-induced ACTH and corticosterone release. PCP (10.0 mg/kg) produced increases in plasma ACTH and corticosterone 60 min after s.c. administration. Pretreatment with naloxone (2.0 mg/kg s.c.) did not reduce the rise in plasma levels of ACTH or corticosterone produced by PCP. These results indicate that naloxone-sensitive opiate receptors are not involved in the PCP-induced stimulation of the pituitary-adrenal axis in rats.

Adrenocorticotropic Hormone↗
PubMed1989

Metaphit antagonizes phencyclidine-induced hypothermia in the rat.

The acute administration of phencyclidine (PCP) causes hypothermia in the rat. Metaphit (1-[1-(3-isothiocyanatophenyl)cyclohexyl]-piperidine) is a derivative of PCP that has been shown to irreversibly acylate PCP receptors in vitro and in vivo and can antagonize the behavioral and electrophysiological effects of PCP in the rat. The purpose of the present study was to determine whether pretreatment with metaphit can block the hypothermic effects of PCP in the rat. Metaphit or PCP (1.0 mumol/rat) were injected into the lateral ventricles of rats, and 24 hr later the subjects were challenged with PCP (20.0 mg/kg s.c.). Pretreatment with metaphit blocked PCP-induced hypothermia; however, pretreatment with PCP did not affect the subsequent hypothermic response to PCP. These results indicate that the antagonism of PCP-induced hypothermia by metaphit was a specific effect and not due to PCP receptor desensitization.

Animals↗