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Biomedical subjects

S W Johnson

Publications and source records attributed to S W Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1989

Ability of periaqueductal gray subdivisions and adjacent loci to elicit analgesia and ability of naloxone to reverse analgesia.

This study is an investigation of the effects of stimulation of regions within and adjacent to the periaqueductal gray (PAG) matter. Eighty-five rats were implanted with 1 monopolar stimulating electrode into 1 of 5 loci. Potency of analgesia was evaluated by relative increases in tailflick latencies after brain stimulation, and threshold current intensity was used to elicit analgesia. The ability of naloxone to reverse the stimulation-induced analgesia was also evaluated. Results replicate the previous finding of differential naloxone reversibility of ventral vs. dorsal PAG sites, but they do not support a regional distinction in the potency of analgesia induced. The results suggest that dorsal PAG sites are involved in a separate nonopiate pain-inhibitory system, whereas ventral sites are involved in an opiate system. These systems, however, do not respect the cytoarchitectural boundaries of the PAG because sites adjacent to the PAG elicit similar effects with a corresponding dorsal-ventral distinction.

Animals↗
PubMed1989

Leisure: how to promote inpatient motivation after discharge.

1. A group of psychiatric inpatients followed plans to participate in leisure activities after discharge at significantly higher levels when treated with classes and written contracts; or classes, written contracts, and musical entertainment; rather than with classes alone. 2. Inpatient classes for psychiatric patients should be coupled with other interventions, such as contracts or musical entertainment, to assist patients to attain therapeutic goals after discharge. 3. The utilization of written goal-setting contracts seems to have merit as a routine nursing intervention with psychiatric inpatients. 4. The use of a written contract left with the patient may promote or enhance a nurse/patient transaction.

Female↗
PubMed1988

Correlation of mutagenic and dermal carcinogenic activities of mineral oils with polycyclic aromatic compound content.

Mutagenicity, polynuclear aromatic compound content, and skin carcinogenicity were compared for a series of complex oil mixtures derived from the refining and processing of petroleum. Mutagenicity in a modified Ames Salmonella assay showed an excellent correlation with carcinogenicity, as determined in a mouse skin-painting bioassay, for oil samples with median boiling points (defined as the temperature at which 50%/volume of an oil sample is recovered as condensate during distillation--50% recovered) above approximately 500 degrees F. A significant correlation was also observed between the 3-7 ring polycyclic aromatic compound (PAC) content and both mutagenic and carcinogenic potencies for samples ranging from those with median (50% recovered) boiling points above approximately 500 degrees F to those with initial boiling points of approximately 1070 degrees F. These results show that both PAC content and mutagenicity are predictive of dermal carcinogenic activity and indicate that PAC components are largely if not entirely responsible for both the carcinogenic and mutagenic activities.

Animals↗
PubMed1986

Structure-activity relationships of phencyclidine derivatives in rat cerebellum.

The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.

Action Potentials↗
PubMed1986

Investigation of the failure of parenterally administered haloperidol to antagonize dopamine released from micropipettes in the caudate.

An anomaly in the experimental data underlying the theory that neuroleptics act by blockade of dopaminergic neurotransmission is the repeatedly demonstrated failure in several laboratories of parenterally administered neuroleptics to antagonize electrophysiologic actions of locally applied dopamine (DA) in striatum. This failure is enigmatic since many investigators have successfully demonstrated antagonism when both dopamine and neuroleptic are applied directly to striatal neurons by microiontophoresis. We used multibarrel micropipettes to pressure-eject DA agonists onto rat caudate neurons while observing the ability of parenterally administered haloperidol to block the inhibitory actions of dopaminergic agonists on neuronal activity. Experiments performed at times of maximal behavioural effect of haloperidol did not demonstrate agonist-antagonist interaction. This result has been obtained by four other teams of investigators. A variety of pharmacologic manipulations were employed to help solve this enigma. Acute treatment with reserpine and alpha-methyl-paratyrosine, performed to minimize any possible interference by endogenous DA, did not permit blockade of dopamine by haloperidol. To see if this failure of antagonism could be generalized to other DA agonists, apomorphine, amphetamine, and phencyclidine (PCP) were also investigated. Although the direct dopaminergic agonist apomorphine was not antagonized by haloperidol, the indirect DA agonist PCP was successfully antagonized. Amphetamine, which has both direct and indirect actions when applied locally, was not antagonized. Antagonism of direct agonists was demonstrated in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. In these preparations, parenterally administered haloperidol reversed the receptor-mediated supersensitivity to the inhibitory effects of locally applied DA and apomorphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1985

Norepinephrine-dependent and independent mechanisms of persistent effects of amphetamine in rat cerebellum.

Previous studies of the effects of chronic low-dose amphetamine (2 mg/kg per day X 21 days) on the spontaneous discharge rate of cerebellar Purkinje neurons have shown persistent depressant effects for up to 50 days after cessation of drug administration. The depression of spontaneous discharge observed was only partially reversible by various pharmacological agents which disrupt noradrenergic neurotransmission in cerebellum. In the present study, several additional approaches were used to investigate further this persistent effect. Rats were treated, either before or after chronic treatment with amphetamine, with intracisternal 6-hydroxydopamine at doses which destroy most noradrenergic fibers in cerebellum. In either case Purkinje neurons were still significantly slowed after cessation of amphetamine treatment, although the depression was not as great as previously observed. In another experiment, cerebellar cortical levels of 3-methoxy, 4-hydroxy phenyl glycol (MHPG) were measured after cessation of amphetamine administration, to determine if there was biochemical evidence for increased noradrenergic neurotransmission. At ten days, MHPG levels were elevated by 36%, and they returned to control values by 30 days. The evidence obtained in these studies suggests that chronic amphetamine treatment causes a persistent increase in noradrenergic neurotransmission, but non-noradrenergic mechanisms may also be important mechanisms in the long-lasting depression of activity of cerebellar Purkinje neurons.

Amphetamine↗
PubMed1984

Presynaptic dopaminergic activity of phencyclidine in rat caudate.

This study tested the hypothesis that phencyclidine (PCP) is an indirect dopamine (DA) agonist in the caudate nucleus. Single caudate neurons in rats anesthetized with urethane were recorded extracellularly with multibarrel micropipettes. Effects of drug solutions, applied by pressure microejection, were measured as changes in spontaneous and evoked neuronal activity. Caudate neurons were classified according to their latency-to-discharge in response to supramaximal cortical stimulation. PCP inhibited the spontaneous activity of 92% of neurons with latencies less than 13 msec, while DA inhibited 87%. Both drugs inhibited evoked activity significantly less than spontaneous activity (P less than .01). Neurons with latencies greater than 13 msec were excited by DA significantly more often (45%) than by PCP (13%; P less than .05). Receptor stereospecificity is suggested by the finding that the (+)-isomer of the 3-methyl piperidine derivative of PCP was significantly more potent than the (-)-isomer for inhibition of spontaneous activity. Mg++, which blocks presynaptic release of neurotransmitter, significantly antagonized inhibitory effects of PCP on spontaneous activity, which suggests a presynaptic effect of PCP. DA, which acts postsynaptically, was much less affected by Mg++. The potency of PCP was significantly less in rats treated with reserpine or 6-hydroxydopamine than in control rats, suggesting the endogenous DA is required for the action of PCP. Fluphenazine and (+)-butaclamol, potent DA-receptor antagonists, blocked the effect of PCP, but (-)-butaclamol did not. These results support the hypothesis that PCP facilitates release and/or inhibits reuptake of DA in nerve terminals and thereby acts as an indirect DA agonist in the caudate. However, there may be a subpopulation of caudate neurons in which PCP acts by a nondopaminergic mechanism.

Animals↗
PubMed1983

Effects of dopamine on spontaneous and evoked activity of caudate neurons.

This study examined the effects of dopamine (DA), pressure ejected from multi-barrelled micropipettes, on the spontaneous and evoked activity of caudate neurons, recorded extracellularly in rats anesthetized with urethane. Neurons were categorized according to their discharge latencies in response to supramaximal cortical stimulation: neurons which fired with latencies less than 13 msec were classified "short-latency-discharge neurons", while neurons with latencies greater than or equal to 13 msec were classified "long-latency-discharge neurons". This procedure also allowed the detection of neurons with low levels of spontaneous activity. The predominant effect of DA on both neuronal types was inhibition of spontaneous activity. However, DA exerted a modulatory effect in that spontaneous activity was inhibited at "doses" which did not affect activity evoked by cortical stimulation. Although DA-induced excitation was infrequent, it was significantly more prevalent among long-latency neurons than among short-latency-discharge neurons. Long-latency-discharge neurons were also significantly more spontaneously active than were short-latency neurons. In rats depleted of endogenous DA by treatment with reserpine, caudate neurons had significantly increased rates of spontaneous and evoked activity, shorter duration of stimulus-evoked inhibition, and longer latency for evoked discharges than in control rats. These results suggest that DA exerts modulatory effects on caudate neuronal activity. Furthermore, these results suggest that short- and long-latency-discharge neuronal groups may consist of pharmacologically, as well as physiologically, distinct neuronal types.

Action Potentials↗
PubMed1982

Persistent effects of amphetamine on cerebellar Purkinje neurons following chronic administration.

The spontaneous discharge of cerebellar Purkinje neurons was studied in rats after withdrawal from chronic treatment with amphetamine (2 mg/kg per day x 21 days). Discharge rates in withdrawn animals remained significantly lower than those of controls for up to 50 days. Disruption of the adrenergic input to these neurons from the locus coeruleus by treatment with propranolol, clonidine or reserpine, partially restored these discharge rates. Acute administration of amphetamine in amphetamine-withdrawn rats did not further depress Purkinje neurons discharge rate, whereas in a previous study in this lab, Purkinje neurons from naive animals were markedly slowed. Moreover, Purkinje neurons from amphetamine-withdrawn rats were also significantly less sensitive than controls to locally applied norepinephrine. These results demonstrate that chronic amphetamine can lead to very long-term changes in neuronal activity, and suggest that these changes may be mediated, in part, by the noradrenergic transmitter systems.

Action Potentials↗
PubMed1982

Dose-response analysis of phenytoin on electrically induced seizures and spontaneous activity of cerebellar purkinje cells in the frog.

The hypothesis that phenytoin exerts its anticonvulsant effect by increasing the spontaneous firing rate of cerebellar Purkinje cells was tested in frogs (Rana pipiens). Time-dose-effect relationships were first established for the anticonvulsant effect of phenytoin in intact frogs. Maximal seizures were induced by corneal electroshock (MES), and phenytoin was injected into the ventral lymph sac. At the time of peak effect (3 h), 20-40 mg/kg phenytoin protected 60-80% of frogs against tonic hindlimb extension (THE). With this functional data base, experiments were then undertaken to test the effect of phenytoin on Purkinje cell firing rates. Phenytoin was injected into the ventral lymph sac 30-45 min prior to anesthesia with tricaine. The cranium was opened, the dura mater overlying the cerebellum was removed, and the frog was then curarized. Single-unit extracellular recordings from Purkinje cells were made with NaCl-filled glass micropipettes 2-6 h after phenytoin injection, the expected time of maximum anticonvulsant effect. Effective anticonvulsant doses (20-40 mg/kg) of phenytoin produced no alteration in the spontaneous firing rates of cerebellar Purkinje cells compared to the rates in solvent-injected controls. Consequently, the hypothesis that the anticonvulsant effect of phenytoin is mediated by an action on Purkinje cell firing rates is not supported by the results of this study.

Animals↗
PubMed1982

Phenytoin antagonism of electrically induced maximal seizures in frogs and mice and effects on central nervous system levels of adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate.

Phenytoin antagonized the electroshock-induced increase in levels of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) in cerebrum and cerebellum, respectively, from CF-1 mice. However, the effective dose range of phenytoin for significant reduction of the elevated levels of cAMP and cGMP was 2 to 5 times higher than that for prevention of tonic hindlimb extension in 95% of mice. The effective dose range of phenytoin for alteration of cyclic nucleotide levels was nearer to that for preventing tonic flexion and clonus; endpoints which are less relevant to anticonvulsant efficacy than is prevention of tonic hindlimb extension. Also , the greatest reduction in cyclic nucleotide levels occurred at a dose (100 mg/kg) which produced toxic signs in mice. Quaking mice (qk/qk), a mutant strain which exhibits spontaneous seizures, did not have abnormal levels of cAMP or cGMP in cerebrum or cerebellum, and a dose of phenytoin (15 mg/kg) which abolished all seizure activity did not alter levels of these cyclic nucleotides. In frogs, the electroshock-associated increase in levels of cAMP in the central nervous system was not altered by phenytoin even when the doses administered were up to twice the ED95 for prevention of tonic hindlimb extension. Because these data from mice and frogs show that the anticonvulsant effect of phenytoin is dissociated, by dose, from effects on central nervous system cyclic nucleotide levels, it is doubtful that the alteration of cyclic nucleotide levels is a mechanism by which phenytoin exerts its anticonvulsant effect

Animals↗
PubMed1982

A comparative study of the effects of phenytoin and phenobarbital on electrically induced maximal seizures in frogs and mice.

This study was undertaken to compare seizure patterns and anticonvulsant effects of phenytoin in frogs (Rana pipiens) and the CF-1 strain of mice. Maximal seizures were induced with electroshock via corneal electrodes, and phenytoin anticonvulsant effects were determined by measuring the duration of tonic hindlimb extension (THE) and prevention of the THE. To control for any possible species difference that might be unique to phenytoin, the anticonvulsant effects of phenobarbital also were compared in frogs and mice. It was found that the dose-effect relationships for shortening THE duration and for prevention of THE by phenobarbital in frogs and mice were not significantly different in terms of slopes and potencies. With phenytoin, however, the dose-effect relationship for prevention of THE in mice was significantly steeper than that in frogs, whereas the slopes of the dose-effect relationships for shortening THE duration were not significantly different in these two species. Frogs decapitated 1.5 sec after electroshock exhibited THE durations equal to those in intact frogs, and phenytoin and phenobarbital efficacies in shortening THE duration were unchanged by decapitation. These results show that shortening of THE duration by both phenytoin and phenobarbital may reflect drug action in spinal or peripheral neural pathways. Also, it is suggested that phenytoin, but not phenobarbital, prevents THE by a selective action on cortical structures which are well developed in mice but are poorly developed or absent in frogs.

Animals↗
PubMed1980

The solubility of phenytoin in a physiological salt solution.

The solubility of phenytoin (PHT) was examined at room temperature (23 degrees C) one hour and 16 hours after solutions were made. PHT was considered to be dissolved if it could be centrifuged at 1500 c g for 30 minutes without loss of supernatant radioactivity produced by 14C-PTH. Radio-labelled PHT dissolved in 50 mM NaOH (pH 12.6) was used as control. One hour after mixing, PHT concentrations greater than 200 microM were incompletely dissolved. Sixteen hours after mixing, concentrations greater than 150 microM were incompletely dissolved. Solutions made with an excess of Na-PHT yielded a supernatant concentration of 105 microM measured 24 hours after mixing. It is concluded that PHT concentrations higher than 105 microM may form supersaturated solutions that remain homogeneous for 16 hours if the total concentration does not exceed 150 microM. The 150 microM solution is considered to be a relatively stable supersaturated solution since the addition of a small amount of Na-PHT caused only a 7% reduction in supernatant radioactivity after 13 hours.

Drug Stability↗