Biomedical subjects

R DeLucia

Publications and source records attributed to R DeLucia.

At least 19 recordsLinked to original sources

PubMed1998

Fencamfamine modulates sodium, potassium-ATPase through cyclic AMP and cyclic AMP-dependent protein kinase in rat striatum.

Dopamine (DA) and fencamfamine (FCF) modulatory action on Na,K-ATPase and Mg-ATPase activity were evaluated in rat striatum. DA and FCF induced a decrease in Na,K-ATPase, without affecting Mg-ATPase activity. The effect of FCF was dose-dependent from 10 to 100 microM, with an IC50 of 4.7 x 10(-5) M. Furthermore, the effect of FCF (100 microM) increasing AMPc levels, but not GMPc, was nonadditive with that of DA (10 microM), which is consistent to a common site of action. The 8-bromo-cyclic AMP also induced a specific reduction in the Na,K-ATPase activity. The reduction of Na,K-ATPase induced by FCF (100 microM) was blocked by either SCH 23390 or sulpiride, which are D1 and D2 receptor antagonists. The decrease in striatal NA,K-ATPase activity induced by FCF was blocked by KT 5720, a selective inhibitor of cyclic AMP-dependent protein kinase (PKA), but not by KT 5823, a selective inhibitor of cyclic GMP-dependent protein kinase (PKG). Otherwise, KT 5720 or KT 5823 did not produce any change in Na,K-ATPase or Mg-ATPase activity. These data suggest that FCF reduces Na,K-ATPase activity through cyclic AMP-dependent changes in protein phosphorylation via a PKA mechanism.

Animals↗

PubMed1998

Involvement of dopamine receptors in diethylpropion-induced conditioning place preference.

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 +/- 39 vs 565 +/- 48 s). Pretreatment with the D1 antagonist SCH 23,390 (0.05 mg/kg, s.c.) 10 min before DEP (15 mg/kg, i.p.) blocked DEP-induced CPP (418 +/- 37 vs 389 +/- 31 s) while haloperidol (0.5 mg/kg, i.p.), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 +/- 36 vs 536 +/- 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP.

Animals↗

PubMed1997

Repeated administration intensifies the reinforcing effect of fencamfamine in rats.

1. In the present study, we evaluated the role of repeated administration on conditioning place preference (CPP) induced by fencamfamine (FCF) in male rats. 2. Repeated FCF (3.5 mg/kg) or saline once or daily for ten consecutive days enhanced sniffing duration and decreased locomotion and rearing duration. 3. At the 3.5 mg/kg dose, FCF produced a significant place-preference effect. 4. Repeated exposures to FCF intensified its reinforcing properties. 5. These results suggest that repeated FCF administration sensitizes its rewarding effects, as with other addictive substances.

Animals↗

PubMed1997

Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices.

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 +/- 4.2 vs 8.4 +/- 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a single dose significantly enhanced the basal motor activity (38.3 +/- 4.5 vs 8.4 +/- 3.5 s) and increased the duration of exploratory activity (38.3 +/- 4.5 vs 32.1 +/- 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and release assays. The inhibition of uptake and release of [3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Animals↗

PubMed1996

The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias.

5-Aminolevulinic acid (ALA), a heme precursor accumulated during the clinical expression of acute intermittent porphyria, lead poisoning, and tyrosinosis, has been hypothesized to act as an endogenous source of oxyradicals. We now report oxidative effects on brain tissue of rats submitted to ALA treatment. Upon acute treatment (40 mg/kg body weight) increased total nonheme iron in the cortex (20%) was observed. After prolonged ALA administration (40 mg/kg body weight on alternate days during 2 weeks), the following indicators of oxidative stress were found to be significantly increased: CuZnSOD activity (67%) in total brain homogenate, total iron (68%) and ferritin (71%) in the cortex, ferritin in striatum (44%), protein carbonyls in homogenate of cerebral cortex (threefold) and 45Ca2+ uptake by cortical synaptosomes (45%). In addition, synaptic membranes prepared from whole brain assayed with the radioligand 3H-muscimol, revealed increased Kd values (twofold) of the high-affinity GABAergic receptor binding and formation of protein carbonyl groups, thiobarbituric acid reactive products, and conjugated dienes. In vitro, ALA produced similar effects upon the high affinity 3H-muscimol binding. No apparent alteration of either dopaminergic or serotonergic [3H]-ligand binding was observed. These results argue in favor of ALA-triggered oxidative stress in brain accompanied by iron metabolism alterations and GABAergic receptor damage, which may be implicated in the neuropsychiatric manifestations of the aforementioned porphyrias.

Aminolevulinic Acid↗

PubMed1995

Reinforcing properties of fencamfamine: involvement of dopamine and opioid receptors.

Fencamfamine (FCF) is a psychostimulant classified as an indirect dopamine agonist. The conditioning place preference (CPP) paradigm was used to investigate the reinforcing properties of FCF. After initial preferences had been determined, animals were conditioned with FCF (1.75, 3.5, or 7.0 mg/kg; IP). Only at the dose of 3.5 mg/kg FCF produced a significant place preference. Pretreatment with SCH23390 (0.05 mg/kg; SC) or naloxone (1.0 mg/kg; SC) 10 min before FCF (3.5 mg/kg, IP) blocked both FCF-induced hyperactivity and CPP. Pretreatment with metoclopramide (10.0 mg/kg; IP) or pimozide (1.0 mg/kg, IP), respectively, 30 min or 4 h before FCF (3.5 mg/kg; IP), which blocked the FCF-induced locomotor activity, failed to influence place conditioning produced by FCF. In conclusion, the present study suggests that dopamine D1 and opioid receptors are related to FCF reinforcing effect, while dopamine D2 subtype receptor was ineffective in modifying FCF-induced CPP.

Animals↗

PubMed1995

The behavioral sensitization induced by fencamfamine is not related to plasma drug levels.

Fencamfamine (FCF) is a CNS stimulant that facilitates central dopaminergic transmission primarily through blockade of dopamine uptake. In the present study we evaluated the relationship between plasma FCF concentration and behavioral sensitization effect. Adult male Wistar rats (250-300 g) received FCF (10 mg/kg, ip) or saline once or daily for 10 consecutive days (N = 10 for each group). Blood samples were collected 30 min after injections and plasma FCF was measured by gas chromatography using an electron capture detector. FCF treatment enhanced sniffing duration (16.8 +/- 0.8 vs 26.6 +/- 0.9 s) and decreased rearing behavior (8.2 +/- 0.8 vs 3.7 +/- 0.6 s) when days 1 and 10 of drug administration were compared. Comparison of pair of means by the Student t-test did not show significant differences in plasma FCF concentration (390 +/- 40 vs 420 +/- 11 ng/ml) when blood samples were collected 30 min after acute FCF administration or after daily administration of 10 mg/kg for 10 days. In conclusion, the behavioral sensitization to FCF could not be correlated with plasma drug levels, and changes in the activity of dopaminergic systems should be considered to explain the sensitization to the effect of FCF.

Animals↗

PubMed1995

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs.

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/kg), fencamfamine (6.0 mg/kg) and cocaine (15.0 mg/kg). Rats received 0.02 mg/kg of apomorphine (sc) and 30 min later were injected with one of the stimulants. Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencamfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behavior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occurred when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied.

Amphetamine↗

PubMed1994

Effects of fencamfamine withdrawal in rats.

1. The effects produced by discontinuation of long-term treatment with fencamfamine (FCF) were evaluated recording behavioral and body weight changes. 2. 48 hr after withdrawal of FCF rats showed a significant decrease in exploratory behavior when compared to saline-treated ones. 3. Discontinuation of treatment with FCF resulted in a significant increase in body weight on days of drug withdrawal. 4. These results suggest that FCF caused signs of withdrawal similar to other psychostimulant drugs.

Animals↗

PubMed1994

Daily variation in plasma concentration of fencamfamine and striatal dopamine receptors in rats.

Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection at 21:00 h. Moreover, at 15:00, 21:00 and 03:00 h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [3H]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation, a phenomenon that should be considered to explain the circadian time-dependent effects of FCF.

Animals↗

PubMed1991

Effect of fencamfamine on avoidance performances of rats.

The effects of fencamfamine (1.0 and 5.0 mg/kg, ip, single dose) on an inhibitory task were studied in rats (N = 15 per group). Post-training treatment with fencamfamine (1.0 mg/kg) significantly increased avoidance latency from 23 +/- 3 to 146 +/- 28 and 170 +/- 33 s for training day 1 and day 7, respectively, indicating an enhancement of retention. However, retention was significantly reduced with a high dose of fencamfamine (5.0 mg/kg). These results demonstrate that fencamfamine caused a reproducible dose-related increase and reduction in avoidance latency.

Animals↗

PubMed1991

Hyperprolactinemia induced by long-term domperidone treatment does not alter the sensitivity of striatal dopamine receptors.

We investigated the effect of hyperprolactinemia induced by long-term domperidone treatment (10.0 mg/kg, single daily dose, ip) on striatal dopamine (DA) receptor sensitivity in male Wistar rats weighing 250-300 g (N = 8). Domperidone treatment for 7 days continued to produce an increase in serum concentration of prolactin (PRL) from 17.3 +/- 2.2 to 33.1 +/- 7.3 and from 16.8 +/- 2.3 to 21.9 +/- 2.1, 2 and 72 h after domperidone withdrawal, respectively. Hyperprolactinemia induced by long-term domperidone treatment did not change binding sites (Bmax) and dissociation constant (Kd) of [3H]-spiroperidol binding when compared to controls. These results show that hyperprolactinemia induced by long-term domperidone treatment does not effect the sensitivity of striatal DA receptors presumably because the effect of neuroleptic drugs is due to their interaction with the receptors and not to the concomitant hyperprolactinemia.

Animals↗

PubMed1990

Carnosine-, calcitonin gene-related peptide- and tyrosine hydroxylase-immunoreactivity in the mouse olfactory bulb following peripheral denervation.

We report the effects of olfactory peripheral deafferentation by intranasal irrigation with ZnSO4 on carnosine and CGRP immunoreactivities in the mouse olfactory system. In the normal rodent olfactory epithelium carnosine immunoreactivity is associated with the olfactory receptor neurons. Conversely, CGRP immunoreactivity appears to be associated with the trigeminal innervation of the nasal cavity. Following lesion the magnitude of carnosine immunoreactivity in the olfactory epithelium is strongly reduced while CGRP immunoreactivity is unaffected. In the olfactory bulb, deafferentation causes a strong reduction of carnosine immunoreactivity in the glomerular layer and, concurrently, of TH immunoreactivity in the juxtaglomerular neurons. CGRP immunoreactive fibers in the olfactory bulb are abundant in the glomerular layer both before and after deafferentation. These data demonstrate that, in the adult mouse, the immunocytochemically detectable levels of CGRP are not altered following lesion and indicate CGRP is not released directly from the olfactory neurons to induce TH production.

Animals↗

PubMed1990

Fencamfamine.

1. Studies on the mechanisms of FCF action using behavioural and biochemical methods have shown that all stimulant effects produced by acute administration of FCF are thought to be due to indirect activation of DA systems in CNS. 2. Changes in the sensitivity of pre- or postsynaptic DA receptors might underlie both tolerance and sensitization to the effects induced by long-term FCF administration.

Animals↗

PubMed1989

Behavioral and neurochemical effects of fencamfamine on rats: a chronobiologic approach.

Fencamfamine (FCF) is a psychostimulant classified as an indirect dopaminergic agonist. Circadian rhythms of some behavioral and neurochemical parameters were investigated in control rats and in rats which had been treated with a single dose of FCF across the 24-hr span. Rats were entrained to light/dark (LD) 12:12, lights on from 0700 to 1900. In behavioral experiments (performed in March) the rats were injected intraperitoneally with saline or FCF (3.5 mg/kg) at one of six times: 0900, 1300, 1700, 2100, 0100 or 0500. Fifteen minutes after treatment the duration of sniffing, rearing and locomotion was recorded during 120 min. Controls showed circadian rhythms for sniffing and rearing with acrophases at 2255 and 0118, respectively. In animals treated with FCF, only locomotion displayed significant circadian variation with acrophase at 1912. Two-way analysis of variance (ANOVA) showed a statistically significant circadian time-dependent effect of FCF on all behavioral parameters studied; the increase of sniffing, rearing and locomotion induced by FCF was higher in rats treated during the rest phase. In the biochemical studies (performed between March-June), rats were treated (i.p.) with saline or FCF (10 mg/kg) at one of four times: 0900, 1700, 2100 or 0100. The levels of homovanillic acid (HVA) in the striatum and tuberculum olfactorium, 5-hydroxyindolacetic acid (5-HIAA) in the cerebellum and 3-methoxy-4-hydroxypheniglycol (MHPG) in the frontal cortex were determined. Controls showed circadian rhythms for HVA (striatum), MHPG (frontal cortex) and 5-HIAA (cerebellum) with acrophases at 2233, 1955 and 1029, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

On the mechanism which mediates the effects of long-term administration of fencamfamine in rats.

This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 +/- 3.2 vs 25.8 +/- 2.8, P less than 0.05) the stereotyped behavior induced by apomorphine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 +/- 0.02 micrograms/g vs 0.31 +/- 0.03 micrograms/g, P less than 0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 +/- 0.04 micrograms/g vs 0.34 +/- 0.03 micrograms/g, P less than 0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine.

Animals↗

PubMed1989

Striatal dopamine receptor supersensitivity after long-term haloperidol treatment of hypophysectomized rats.

Dopamine (DA) receptor sensitivity was studied after long-term treatment with haloperidol (0.5 and 3.0 mg/kg, ip, single daily dose) or saline in hypophysectomized and intact rats. Haloperidol treatment for seven days produced a 25 to 125% increase in [3H]-spiroperidol binding to striatal DA receptors in a dose-dependent fashion. The increase in binding sites (Bmax) was similar in both hypophysectomized and intact rats when compared to controls. The present results show that hypophysectomy does not effect the supersensitivity of striatal DA receptors induced by long-term haloperidol treatment.

Animals↗

PubMed1988

Psychostimulant effects of fencamfamine in healthy volunteers.

The effects of fencamfamine (25 and 50 mg po) were studied on acute psychophysiological and psychomotor performance in six healthy male volunteers. Stimulant effects, such as greater increases of critical flicker-fusion threshold, heart rate, blood pressure and stimulation assessed by self-rating, were more pronounced with the higher dose of fencamfamine. Paradoxical sedative effects were obtained with the 25 mg dose. Fencamfamine should not be considered only as an energizing agent, but also as an agent having a psychostimulant profile of effects.

Administration, Oral↗