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J Peris

Publications and source records attributed to J Peris.

32 records · Page 2Linked to original sources
PubMed1988

Sensitization to cocaine in the nigrostriatal dopamine system.

Behavioral sensitization involving the nigrostriatal dopaminergic tract is manifested after treatment with only a single dose of cocaine and is augmented following repeated treatment. One neurochemical change observed that is consistent with behavioral sensitization is the increase in amphetamine-induced 3H-DA release from striatal slices seen after one injection of cocaine. One day after repeated administration of cocaine, however, the increase is no longer evident. It is possible that transient compensatory changes, such as increased D-2 autoreceptor inhibition, may obscure this effect when it is measured at relatively short times after the repeated administration has been terminated. One day after cessation of repeated cocaine administration, D-2 autoreceptors in both striatum and substantia nigra compacta were upregulated consistent with a compensatory mechanism and the development of behavioral tolerance rather than sensitization. In contrast, DA content, neuronal DA uptake, and postsynaptic D-2 DA receptors in striatum were not regulated by this treatment. Likewise, D-1 DA receptors in striatum and substantia nigra were unaffected. In the mesolimbic system, both the pre- and postsynaptic receptor changes are consistent with sensitization. Amphetamine-stimulated release from nucleus accumbens has not yet been measured in cocaine-sensitized animals. It is possible that changes similar to those seen in striatum may occur in this area. It is interesting that, in general, presynaptic parameters associated with the DA neuron, with the notable exception of the uptake pump, appear to be more sensitive to regulation by cocaine administration than do postsynaptic parameters. The long-lasting effects of a single moderate dose of cocaine are also surprising. It will be important to determine the molecular mechanisms underlying this regulation and whether or not similar changes are induced in mesolimbic dopaminergic systems by single and repeated administration of cocaine.

Animals↗
PubMed1987

Modulation of gamma-[3H]aminobutyric acid release from rat cortical slices by alpha 2-adrenoceptors.

Modulation of gamma-aminobutyric acid (GABA) release by alpha 2-adrenoceptor agonists has not been consistently demonstrated. This could be due to high levels of norepinephrine (NE) concomitantly evoked by stimulation parameters needed for GABA release. In the present experiments, NE release was preferentially decreased by omission of calcium (Ca2+) and alpha 2-modulation of [3H]GABA release from cortical slices was measured. The antagonist rauwolscine increased only Ca2+-dependent [3H]GABA release, while the agonists guanabenz and clonidine inhibited only Ca2+-independent GABA release. These results suggest that release of endogenous NE diminished the effect of alpha 2-agonists but reveals the effect of antagonists and support the hypothesis that endogenous NE inhibits GABA release in cortex.

Animals↗
PubMed1987

One injection of cocaine produces a long-lasting increase in [3H]-dopamine release.

A single cocaine exposure has been reported to sensitize animals to the behavioral effect of subsequent cocaine administration for up to one week. We now report that a single injection of cocaine results in an augmentation in amphetamine-induced release of tritium from rat striatal slices preloaded with [3H]-dopamine. The augmentation appears within 24 hr and persists for at least 2 weeks after injection. This increase in release may result in increased synaptic concentrations of dopamine possibly caused by a change in the membrane transporter for dopamine. Increased dopaminergic synaptic transmission could explain behavioral sensitization.

Animals↗
PubMed1987

Effects of restraint and naltrexone on the biphasic heart rate response to morphine in rats.

The effect of several doses of morphine (0, 0.5, 2, 5 or 10 mg/kg, i.v.) on heart rate was assessed in restrained and freely-moving rats. Morphine produced a dose-dependent bradycardia followed by tachycardia. The magnitude and duration of bradycardia were greater in restrained rats, whereas the magnitude and duration of tachycardia were greater in unrestrained rats. Naltrexone (5 mg/kg) pretreatment completely blocked the biphasic heart rate response to morphine (8 mg/kg). When naltrexone was given after the bradycardic portion of the response, tachycardia declined to baseline levels. These results suggest that one or both components of the biphasic response are mediated by opioid receptors.

Animals↗
PubMed1987

Stress enhances the development of tolerance to the hypothermic effect of ethanol.

Handling procedures used for body temperature measurement in rats, such as repeated rectal probing during restraint, raise body temperature in a manner similar to other stressors. Thus, the common use of this procedure to monitor temperature may actually obscure the results of experiments measuring the acute and chronic effects of alcohol. In the present experiment, temperature was continuously monitored with implanted biotelemetric sensors, thus eliminating the need for repeated stressful handling. Handling stress was found to interact with the effects of ethanol intoxication to augment the initial hypothermic effect of ethanol. Moreover, the rate and extent of tolerance development to ethanol-induced hypothermia was enhanced.

Animals↗
PubMed1986

[Electron microscopic microanalysis of prickle cell carcinoma, basaloma, malignant melanoma and normal skin].

EMMA has been used in Dermatology since 10 years. In 1981, Fisher established the Cu/Zn index as a parameter for the prognosis of malignant melanoma. We tested the EMMA technique as a means to determine the Cu/Zn index in basal cell carcinoma, squamous cell carcinoma, malignant melanoma, and normal skin. Our preliminary conclusions are: EMMA may be useful to determine the Cu/Zn index in skin tumors; it is possible to obtain useful data from tumors already fixed in paraffin; (c) the highest Cu/Zn index was found in normal skin, the lowest one in malignant melanoma.

Basal Cell Carcinoma↗
PubMed1986

Handling-induced enhancement of alcohol's acute physiological effects.

A mild stressor (handling) exacerbated the acute effects of ethanol on heart rate and body temperature in rats. Although the tachycardia produced by the combination of ethanol and handling appeared to be due to a simple summation of the separate tachycardic effects of each condition, the thermal change represented a nonadditive combination of the separate effects. Specifically, although handling alone produced hyperthermia, it enhanced the hypothermia induced by ethanol. Blood and brain levels of ethanol were not altered by handling. Stress-induced enhancement of critical responses to ethanol may have important implications for the development of tolerance to and dependence on alcohol.

Alcoholic Intoxication↗
PubMed1986

Heart rate response to shock delivered via different implanted electrodes.

The heart rate reaction elicited by electric shock was studied in rats stimulated via implanted electrodes that were placed entirely beneath the skin (subcutaneous electrodes) or were passed under and through the skin (cutaneous electrodes). Cutaneous shock elicited greater cardioaccelerations than subcutaneous shock except at very low intensities. This finding may help to explain differences in conditioned heart rate responses when these two types of electrodes are used to deliver shock stimuli.

Animals↗
PubMed1985

Barbiturate tolerance and dependence: effects on synaptosomal sodium transport and membrane fluidity.

DBA mice were fed lab chow containing phenobarbital for seven or eight days. Upon withdrawal of the phenobarbital diet, dependence was evidenced by appearance of hypothermia, handling-induced convulsions and lethal seizures. Functional tolerance was determined by injecting phenobarbital into mice treated with the phenobarbital diet or a pair-fed control diet and measuring the brain concentration of phenobarbital at the time of loss of righting reflex and the time of regaining righting reflex. Both measures demonstrated that chronic consumption of phenobarbital resulted in functional tolerance. When the diet was withdrawn for two days, tolerance was no longer present, indicating a rapid reversal of the adaptive changes. The veratridine-stimulated uptake of 24Na by isolated brain synaptosomes was used as a measure of membrane function. Sodium uptake was inhibited in vitro by pentobarbital and ethanol, and the inhibitory effects of these drugs were attenuated by chronic in vivo phenobarbital treatment. The fluidity of brain synaptic plasma membranes was estimated by the fluorescence polarization of the fluorescent probe molecules 1-(4-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene and 1,6-diphenyl-1,3,5-hexatriene. Synaptic membranes from mice treated chronically with phenobarbital did not differ from those of control mice with regard to either the baseline fluorescence polarization of the probes or the decrease in fluorescence polarization produced by in vitro exposure to phenobarbital or ethanol. Taken together, these results indicate that although chronic phenobarbital ingestion resulted in tolerance and dependence (studied in vivo), and adaptation of sodium channels (studied in vitro), there was no evidence that these changes were due to alterations in the membrane physical properties.

Animals↗
PubMed1985

Dissociation of tolerance to the hypothermic and tachycardic effects of ethanol.

Tolerance to the cardioacceleratory and hypothermic effects of ethanol was studied in unanesthetized, freely-moving rats surgically implanted with EKG electrodes and biotelemetric temperature sensors. Different groups received 0.0, 1,0 or 2.0 g ethanol/kg body weight in injections given every other day for a total of nine injections. Heart rate and body temperature were recorded for 1 hr before and 2 hr after each injection. Ethanol initially induced a monophasic dose-related cardioacceleration (80 bpm) and hypothermia (1.0 degrees C) that persisted throughout the 2-hr sample period. Tolerance developed to the hypothermic, but not to the tachycardic effect of ethanol. Assuming that tolerance depends on level of impairment in specific neuronal pathways, this outcome suggests that these two effects of ethanol are not mediated through a common autonomic mechanism (e.g., vasomotor depression) and/or that tolerance to the hypothermic effect is due to alterations in pathways unique to the thermoregulatory system. Overall, the finding is consistent with those of studies showing development of tolerance to depressant, but not to excitatory drug effects.

Animals↗
PubMedDate not supplied

Creatine kinase release from isolated EDL muscles in chronic ethanol-treated rats.

Chronic ethanol abuse has been shown to cause damage to skeletal muscle in animals and patients as reflected by elevated serum levels of cytosolic enzymes and histological examination. The present study investigated the hypothesis that elevated serum creatine kinase levels in ethanol-treated animals vs. sucrose control animals may result from increased enzyme release or efflux from muscle. Creatine kinase release was measured from extensor digitorum longus (EDL) muscles isolated from rats chronically treated for 28 weeks with ethanol and from sucrose fed controls. The in vitro cumulative release of creatine kinase over a 2-h period was significantly higher in the ethanol-treated animals. Consistent with an increased release of enzyme into the bath, creatine kinase levels in muscle homogenates at the end of the incubation period were lower in the ethanol-treated animals. Creatine kinase levels in serum obtained from trunk blood samples were statistically higher in the ethanol-treated animals compared to sucrose controls. These findings demonstrate increased enzyme release from fast-twitch skeletal muscle in chronic ethanol-treated rats.

Animals↗
PubMedDate not supplied

Inhibitory neuromodulation of release of amino acid neurotransmitters.

Many drugs of abuse (opiates, cocaine, amphetamine, caffeine) modulate or interact with neurotransmitter systems in the brain (e.g., opiate, dopaminergic, adrenergic, purinergic), generally in an inhibitory fashion. However the cellular mechanisms underlying these interactions are varied and often not well-characterized. A summary of the literature on the neuromodulation of two amino acid neurotransmitters (gamma-aminobutyric acid, glutamate) by these drugs and their analogs may contribute to the understanding of the mechanisms underlying inhibitory neuromodulation. In addition, the types of experiments needed to alleviate some of the problems in this area are outlined.

Adenosine↗