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S D Gleason

Publications and source records attributed to S D Gleason.

11 recordsLinked to original sources
PubMed2004

Effects of dopamine D1 receptor full agonists in rats trained to discriminate SKF 38393.

Although the dopaminergic pharmacology of the D1 receptor full agonists, dinapsoline, dihydrexidine and the prodrug ABT-431 have been studied, no information is available on the ability of these agonists to substitute for the D1 agonist SKF 38393 in rats trained to discriminate this compound from vehicle. The present study was designed to characterize the potential D1 discriminative stimulus effects of these compounds. The selective dopamine D1-receptor agonists dihydrexidine [(+/-)-trans-10,11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine hydrochloride], ABT-431 [(-)-trans-9,10-diacetyloxy-2-propyl-4,5,5a,6,7,11b-hexahydro-3-thia-5-azacyclopent-1-ena[c]phenanthrene hydrochloride], the diacetyl prodrug derivative of A-86929, and dinapsoline [9-dihydroxy-2,3,7,11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline] were studied in rats trained to discriminate racemic SKF 38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol], a selective D1 receptor partial agonist from vehicle. All of the agonists substituted fully for the discriminative stimulus effects of SKF 38393. The rank order of potency for substitution was ABT-431 > dinapsoline > dihydrexidine > SKF 38393. The D1 receptor antagonist, SCH 23390, blocked the discriminative stimulus effects of SKF 38393. The D3/D2-receptor agonist PD 128,907 [S(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]-benzopyrano[4,3-b]-1,4-oxazin-9-ol] did not substitute up to doses that produced profound rate-suppressant effects. Thus, consistent with their D1 receptor pharmacology, the full D1-receptor agonists substituted completely for the discriminative stimulus of SKF 38393.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

m-CPP hypolocomotion is selectively antagonized by compounds with high affinity for 5-HT(2C) receptors but not 5-HT(2A) or 5-HT(2B) receptors.

The ability of m-CPP [1-(m-chlorophenyl)piperazine] to produce hypolocomotion is well documented. This effect has been postulated to be due to activation of the 5-HT(2C) receptor. It is only recently that the tools necessary to clearly delineate which serotonin receptors are involved in the mediation of m-CPP hypolocomotion have become available. We investigated the effects of the selective 5-HT(2A) antagonists, MDL 100,907 and ketanserin, the selective 5-HT(2B) antagonists, LY 202146 and LY 266097, the 5-HT(2B/2C) antagonist, SB 206553, and the selective 5-HT(2C) antagonist, SB 242084 on m-CPP-induced hypolocomotion and spontaneous locomotor activity in mice. Furthermore, we investigated the effects of the non-selective serotonin antagonists, ritanserin, LY 53857, mianserin and cyproheptadine on m-CPP hypolocomotion. Additionally, receptor-binding studies were employed as an in vitro assessment of relative affinities at the 5-HT(2A), 5-HT92B) and 5-HT(2C) receptors. Antagonists tested alone were without effect on spontaneous activity, with the sole exception of ketanserin, which decreased spontaneous activity at the high dose of 1 mg/kg. m-CPP-induced hypolocomotion was not significantly attenuated by various doses of MDL 100,907, ketanserin, LY 202146, LY 266097, ritanserin or cyproheptadine. In contrast, SB 206553, SB 242084, LY 53857 and mianserin were capable of reversing m-CPP-induced hypolocomotion. Consistent with previous suggestions, a detailed pharmacological evaluation with selective antagonists for the 5-HT2 family of receptors supports a primary role for the 5-HT(2C) receptor, and not 5-HT(2A) or 5-HT(2B) receptors, in mediating the hypolocomotion produced by m-CPP.

Amphetamines↗
PubMed1999

Influence of light cycle on response to 5-HT1A ligands in punished responding in rats.

Since the introduction of buspirone, the 5-HT1A receptor has been a focal point for serotonergic research into the treatment of anxiety. Two of the more commonly used methodologies for evaluating potential anxiolytics are the Geller-Seifter model and the elevated plus maze. In the Geller-Seifter model, administration of 5-HT1A agonists produce an anxiolytic-like profile consisting of an increase in the number of responses made during the punished component. An anxiolytic-like response in the elevated plus maze consists of an increase in the number of entries and/or time spent in the open arms of the maze. Recently, there have been reports of differential drug effects with 5-HT1A ligands in the elevated plus maze depending on when in the diurnal cycle the 5-HT1A agents were administered. The purpose of the current study was to characterize the response to 5-HT1A compounds in normal and reverse light cycle animals in the Geller-Seifter model. 8-OH-DPAT [(+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronapthalene] produced a decrease in unpunished responding and an increase in punished responding during both the light and dark phase. The administration of WAY 100,635 [N-¿2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl¿-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloridel alone was without effect in both the light and dark phase. Furthermore, pre-treatment with WAY 100,635 completely antagonized both the rate-decreasing effects in the unpunished component and the increase in punished responding observed with 8-OH-DPAT during both the light and dark phase. The results of the current study diverge from previous findings of sensitivity to the diurnal cycle in other models reflective of modulation of the 5-HT1A receptor. The robustness of the response, in this case punished lever pressing, may be less sensitive than other more naturalistic or ethological methods (i.e. elevated plus maze) in detecting the subtle changes in receptor function due to the diurnal cycle.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Meta-chlorophenylpiperazine induced changes in locomotor activity are mediated by 5-HT1 as well as 5-HT2C receptors in mice.

1-(Meta-chloro)phenylpiperazine (m-CPP) is a 5-HT receptor agonist which has been purported to be relatively selective for the 5-HT2C receptor. In particular, the hypolocomotion produced by m-CPP has been suggested to be mediated by 5-HT2C receptors. m-CPP binds with high affinity to 5-HT1 as well as 5-HT2 receptors, thus effects of m-CPP on locomotor activity may be due to the physiologic summation of the actions of m-CPP at 5-HT1 as well as 5-HT2 receptors. The present study investigated the effects of m-CPP alone and in the presence of the 5-HT2 receptor antagonist 6-methyl-1-(-methyethyl)-ergoline-8beta-carboxylic acid 2-hydroxy-1-methylpropyl ester maleate (LY53857), the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-N-(2pyridinyl)c yclohexanecarboxamide trihydrochloride (WAY 100,635), and the 5-HT(1B/1D) receptor antagonist 2'-methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-corbox ylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]amide (GR 127935) on locomotor activity. Administration of m-CPP alone (0.3-10 mg/kg) produced a dose-related decrease in locomotor activity. The 5-HT(1B/1D) receptor antagonist GR 127935 (3.0 mg/kg) in combination with m-CPP produced a slight leftward shift of the dose-response curve of m-CPP. The 5-HT1A receptor antagonist WAY 100,635 (1.0 mg/kg) in combination with m-CPP did not alter the m-CPP dose-response curve. The non-selective 5-HT2 receptor antagonist LY53857 (1.0 mg/kg) in combination with m-CPP unmasked a hyperlocomotion produced by m-CPP. Furthermore, the hyperlocomotion produced by m-CPP in the presence of LY53857 (1.0 mg/kg) was blocked by both the 5-HT(1B/1D) receptor antagonist GR 127935 (3.0 mg/kg) and the 5-HT1A receptor antagonist WAY 100,635 (1.0 mg/kg). The present results demonstrate that the hyperlocomotion seen with the combination of m-CPP and LY53857 is mediated by 5-HT1 receptors. Taken together the data indicate that m-CPP affects locomotor activity by the physiologic summation of agonist activity at the 5-HT2C receptor as well as the 5-HT1 receptor family.

Animals↗
PubMed1997

Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice.

In humans, phencyclidine (PCP) is known to produce a syndrome of behavioral effects which have many characteristics in common with schizophrenia. Therefore, antagonism of PCP effects might be evidence for antipsychotic efficacy of a compound. In the present studies, the effects of the D2-like antagonist haloperidol, the mixed D2-like/5-HT2 antagonists olanzapine and clozapine, and a series of 5-HT receptor subtype selective antagonists on the hyperlocomotion produced by PCP were evaluated in mice. PCP (0.3-10 mg/kg) produced a dose-related increase in locomotor activity, with a peak effect at 3.0 mg/kg. The D2-like antagonist haloperidol produced a dose-related decrease in locomotor activity when administered alone, and blocked the hyperactivity effects of PCP over the same dose-range (minimal effective dose, MED = 0.3 mg/kg for both effects). In contrast, olanzapine and clozapine reversed the hyperlocomotion effects of PCP at doses (MED = 0.03 and 0.3 mg/kg, respectively) approximately 30- and 10-fold, respectively, below those that decreased activity when administered alone (MED = 1.0 and 3.0 mg/kg, respectively). The selective 5-HT2 antagonist LY53857 (0.3-3.0 mg/kg) administered alone had no effect on locomotor activity but reversed (MED = 0.1 mg/kg) the effects of PCP. Similarly, the selective 5-HT2A/2C antagonist ritanserin (0.001-1.0 mg/kg) alone had no effect on locomotor activity, but reversed (MED = 0.01 mg/kg) the effects of PCP. The selective 5-HT2A antagonists ketanserin (MED = 3.0 mg/kg) and MDL 100,907 (MED = 0.3 mg/kg) produced dose-related decreases in locomotor activity and ketanserin (MED = 0.1 mg/kg) and MDL 100,907 (MED = 0.003 mg/kg) reversed the effects of PCP. The selective 5-HT3 antagonist zatosetron (0.01-10 mg/kg) and the selective 5-HT1A antagonist WAY 100,635 (0.001-3 mg/kg) were without effects on spontaneous locomotor activity. Zatosetron reversed the effects of 3.0 mg/kg PCP at the nonselective dose of 10 mg/kg whereas WAY 100,635 (0.001-1 mg/kg) did not affect PCP-induced hyperlocomotion. The present results indicate that PCP increases locomotor activity, at least in part, due to actions at 5-HT2A, but not 5-HT3 or 5-HT1A, receptors. Further, the present findings support the hypothesis that antagonism at 5-HT2A receptors contributes to the in vivo actions of atypical antipsychotics such as olanzapine and clozapine.

Animals↗
PubMed1997

Behavioral pharmacology of olanzapine: a novel antipsychotic drug.

BACKGROUND: In this paper, we review the behavioral pharmacology of olanzapine and compare it to its in vitro profile and to clozapine and a number of other antipsychotic agents, and we estimate the likelihood that olanzapine will be an effective and safe antipsychotic with fewer side effects. METHOD: Since there is no model of schizophrenia, per se, a battery of behavioral assays was used. RESULTS: Behavioral assays confirmed the in vitro results that olanzapine interacts with dopamine, serotonin, and muscarinic receptor subtypes. Moreover, olanzapine appears to have a clozapine-like atypical profile based on (1) mesolimbic selectivity, (2) blocking 5-HT receptors at a lower dose than dopamine receptors, and (3) inhibiting the conditioned avoidance response (indicative of antipsychotic efficacy) at doses that are lower than those required to induce catalepsy (indicative of extrapyramidal side effects). No only is this profile similar to that of clozapine, but olanzapine has other similarities: olanzapine substitutes for clozapine in a drug discrimination assay; like clozapine and unlike "typical" antipsychotics, olanzapine increases responding in a conflict procedure; and olanzapine, like clozapine, reverses changes induced by antagonists of the NMDA receptor. CONCLUSION: On the basis of these findings, we predict that olanzapine will be an efficacious antipsychotic, active against both positive and negative symptoms, while producing fewer extrapyramidal symptoms than existing treatments.

Animals↗
PubMed1991

Nutrient, waste management, and hygiene systems for chemical protective suits.

Current United States military chemical protective ensembles do not provide for feeding, removing body wastes, or ensuring the hygiene of troops operating in a contaminated environment. As part of a nuclear-biological-chemical life support demonstration program, systems were developed to provide these capabilities. The nutrient system consisted of foods packaged in tube dispensers and a delivery system compatible with North Atlantic Treaty Organization respirators. The waste management/hygiene systems consisted of waste collection and hygiene items incorporated into a retractable-arm suit design with integrated airlock. A field demonstration of the systems resulted in successful use by armored vehicle personnel, high, positive user feedback, and only minor functional problems.

Chemical Warfare↗
PubMed1982

Dietary sodium intake: a determinant of postprandial plasma sodium concentration in the dog.

1. The effect of dietary sodium intake on pre- and post-prandial plasma sodium concentrations and on the pattern of sodium and potassium excretion was determined in conscious female dogs, who were allowed free access to water and were fed on commercial low sodium diets supplemented with 0, 50, 100 or 250 mmol of sodium chloride/day for 6 days. 2. The preprandial plasma sodium concentration was not altered by the dietary sodium intake. However, the 4 h postprandial plasma sodium concentration was linearly related to the magnitude of dietary sodium intake, whereas the 8 h postprandial plasma sodium concentration was elevated only in dogs receiving 250 mmol of sodium/day. 3. The (0-8 h/0-24 h) ratio for urinary sodium excretion was significantly correlated with both the dietary sodium intake and the postprandial increase in plasma sodium concentration. 4. The 24 h excretion of potassium was not markedly affected by the dietary sodium intake; however, the (0-8 h/0-24 h) ratio for potassium excretion was significantly correlated with both the dietary sodium intake and the (0-8/0-24 h) ratio for sodium excretion. 5. These data indicate that: (a) postprandial increases in plasma sodium concentration need to be considered when evaluating the mechanisms involved in the daily regulation of sodium balance; (b) the daily pattern of potassium excretion is closely linked to the dietary sodium intake.

Animals↗
PubMed1982

Renal and endocrine response to water deprivation in dog.

Plasma and urine sodium, potassium, osmolality, aldosterone, and plasma renin activity (PRA) were measured in time controls and during control dehydration and rehydration periods in conscious dogs fed a 50 mmol NaCl diet. During 4 days of water restriction, plasma sodium and osmolality and PRA were elevated, whereas plasma potassium and aldosterone were not affected. Urinary potassium excretion was elevated above intake levels during the entire dehydration period, whereas Na excretion was only elevated during the first 2 days of dehydration. Unrestricted rehydration was associated with a marked fall in plasma sodium and osmolality, a decrease in PRA, and no change in plasma potassium or aldosterone. In addition, during the 1st day of rehydration, there was marked retention of sodium and potassium. Thus, in the dog, dehydration and subsequent rehydration cause significant alterations in sodium and potassium balance and marked alterations in PRA that are not associated with changes in either plasma aldosterone concentration or urinary aldosterone excretion.

Aldosterone↗
PubMed1981

Lack of evidence for gastrointestinal control of sodium excretion in unanesthetized rabbits.

Experiments were performed to determine whether unanesthetized rabbits exhibit a greater natriuresis after oral administration of a hypertonic sodium chloride solution (1.5 mmol NaCl/kg) than after the intravenous administration of the same solution. Male rabbits (New Zealand) were placed on a low sodium diet for 4 days, and on the fifth day a hypertonic NaCl solution (616 mM) was given either by stomach tube (GI) or intravenously (IV), while an equal volume of a hypotonic NaCl solution (31 mM) was given by the alternate route. The studies were repeated on each rabbit so that paired observations were obtained. No differences in plasma Na concentration, peripheral hematocrit, or urinary sodium excretion were observed between the GI and IV groups after administration of the hypertonic NaCl solution. In seven rabbits that were permitted access to food and water following NaCl administration by either route, urinary sodium excretion tended to be reduced (P = 0.08), but, again, no significant differences in plasma sodium concentration, peripheral hematocrit, or urinary sodium excretion were observed between the GI and IV routes of sodium administration. Accordingly, we could find no evidence to support the existence of a GI or portal Na receptor system that regulates urinary sodium excretion in the unanesthetized rabbit.

Administration, Oral↗