Résumé
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 sigle 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.
Sujets)
Rats , Animaux , Mâle , Comportement/effets des médicaments et des substances chimiques , Stimulants du système nerveux central/pharmacologie , Rythme circadien/effets des médicaments et des substances chimiques , Corps strié/métabolisme , Dopamine/biosynthèse , Dopamine/métabolisme , Monoterpènes de type norbornane/pharmacologie , Rat WistarRésumé
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 fencmfamine 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 behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured 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
Sujets)
Animaux , Mâle , Rats , Amfétamine/pharmacologie , Apomorphine/pharmacologie , Stimulants du système nerveux central/pharmacologie , Cocaïne/pharmacologie , Activité motrice/effets des médicaments et des substances chimiques , Monoterpènes de type norbornane/pharmacologie , Amfétamine/administration et posologie , Analyse de variance , Apomorphine/administration et posologie , Comportement animal/effets des médicaments et des substances chimiques , Stimulants du système nerveux central/administration et posologie , Cocaïne/administration et posologie , Monoterpènes de type norbornane/administration et posologie , Rat WistarRésumé
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
Sujets)
Animaux , Mâle , Rats , Rythme circadien , Monoterpènes de type norbornane/sang , Récepteurs dopaminergiques/métabolisme , Acide homovanillique/métabolisme , Chromatographie en phase gazeuse , Rythme circadien/effets des médicaments et des substances chimiques , Corps strié/effets des médicaments et des substances chimiques , Corps strié/métabolisme , Injections péritoneales , Monoterpènes de type norbornane/administration et posologie , Monoterpènes de type norbornane/pharmacologie , Rat Wistar , Spipérone/métabolisme , Facteurs tempsRésumé
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 ñ 3 to 146 ñ 28 and 170 ñ 33 s for training day 1 and day 7, respectively, indicating an enhacement 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
Sujets)
Rats , Animaux , Mâle , Apprentissage par évitement/effets des médicaments et des substances chimiques , Réaction de fuite/effets des médicaments et des substances chimiques , Monoterpènes de type norbornane/pharmacologie , /effets des médicaments et des substances chimiques , Catécholamines/métabolisme , Relation dose-effet des médicaments , Rat Wistar , Temps de réaction/effets des médicaments et des substances chimiquesRésumé
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 + or - 3.2 vs 25.8 + or - 2.8,P<0.05) the stereotyped behavior induced by apomorfhine (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 + or - 0.02 micron g/g vs 0.31 + or - 0.03 microng/g, P<0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 + or - 0.04 microng/g vs 0.34 + or - 0.03 microng/g, P<0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine
Sujets)
Rats , Animaux , Mâle , Apomorphine/antagonistes et inhibiteurs , Stimulants du système nerveux central/pharmacologie , Monoterpènes de type norbornane/pharmacologie , Comportement stéréotypé/effets des médicaments et des substances chimiques , Corps strié/effets des médicaments et des substances chimiques , Incompatibilité médicamenteuse , Tolérance aux médicaments , Monoterpènes de type norbornane/administration et posologie , Lignées consanguines de rats , Récepteurs dopaminergiquesRésumé
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 thereshold, heart rate, blood pressure and stimulation assessed by self-rating, were more pronounced with the higher dose of fencamfamine. Paradoxical sedative effects were obrained 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
Sujets)
Adulte , Humains , Mâle , Fréquence critique de fusion/effets des médicaments et des substances chimiques , Hémodynamique/effets des médicaments et des substances chimiques , Monoterpènes de type norbornane/pharmacologie , Performance psychomotrice/effets des médicaments et des substances chimiques , Administration par voie orale , Essais cliniques comme sujet , Relation dose-effet des médicaments , Méthode en double aveugle , Tests psychologiquesRésumé
Nesta revisäo säo apresentados os prováveis mecanismos de açäo das drogas psicoestimulantes, tendo como padräo a anfetamina. Säo revistos também resultados obtidos com os estudos sobre a fencanfamina (Reactivan), um estimulante utilizado abusivamente em nosso meio. A administraçäo dessas drogas aumenta a liberaçäo de dopamina de ambos os reservatórios celulares de armazenamento. Estes efeitos säo dose-dependentes e multifásicos e, portanto, de difícil interpretaçäo em termos funcionais da transmissäo dopaminérgica