RESUMO
Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) caused a lesion in the substantia nigra, compact part (SNc) and a specific loss of dopamine and its metabolites in the striatum of rats. The animals were then tested in the two-way active avoidance task. MPTP-treated animals presented lower learning scores in the training and test sessions, an effect that was not caused by motor impairment or by a decreased sensitivity to footshock since their reaction time to the footshock (unconditioned stimulus - UCS) was not reduced. These lower scores were also not attributable to lower acoustic sensitivity or to a slowing in the association of the sound cue (conditioned stimulus - CS) with the UCS since the reaction time to the CS in the active avoidance response did not differ between MPTP-treated and control groups. Therefore, these results are more properly attributable to an impairment of the memory acquisition and retention processes. In addition, this study is presented as a model of early Parkinson's Disease amnesia and is discussed in terms of the importance of the nigrostriatal pathway to memory acquisition and storage processes.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Aprendizagem da Esquiva/efeitos dos fármacos , Rememoração Mental/efeitos dos fármacos , Transtornos Parkinsonianos/induzido quimicamente , Substância Negra/efeitos dos fármacos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Aprendizagem por Associação/efeitos dos fármacos , Aprendizagem por Associação/fisiologia , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Dopamina/metabolismo , Masculino , Rememoração Mental/fisiologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos Wistar , Retenção Psicológica/efeitos dos fármacos , Retenção Psicológica/fisiologia , Substância Negra/fisiopatologiaRESUMO
The present study was carried out to test the possible effects of caffeine in improving the memory deficits observed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP)-lesioned rats, an animal model of early stage Parkinson's disease. Caffeine at the doses of 0.1-0.3 mg/kg (intraperitoneal) reversed the impairing effect of the administration of MPTP (1 micromol/side) into the substantia nigra, compact part, of rats on the avoidance scores in the training and test sessions of a two-way active avoidance task. This effect was not due to a motor or sensory alteration because the caffeine-induced learning and memory improvement was independent of the locomotor stimulant effect of the drug and there were no differences in the reaction time of the animals to a footshock (unconditioned stimulus) or a sound cue (conditioned stimulus) after caffeine treatment. These results suggest that the reported dopamine/adenosine-receptor interaction can be used to restore defective learning and memory processes in Parkinson's disease and indicate that caffeine and other adenosine receptor antagonists are drugs with the potential for treatment of the cognitive disabilities of Parkinson's disease.
Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Transtornos da Memória/tratamento farmacológico , Transtornos Parkinsonianos/complicações , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Dopaminérgicos/farmacologia , Relação Dose-Resposta a Droga , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/fisiopatologia , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos Wistar , Substância Negra/efeitos dos fármacos , Substância Negra/fisiopatologiaRESUMO
We have previously observed that the combination of ethanol (EtOH) and the anorectic drug mazindol (MZ) produces more marked effects on behavior than either substance alone. In the present study we examined whether the repeated administration of the drug combination could induce sensitization to its motor activating effects in mice and, if so, whether this response could be affected by dopamine (DA) receptors antagonists. Male Swiss albino mice were treated daily for 7 days with combined EtOH+MZ (1.2 g/kg, 5.0 mg/kg IP), EtOH (1.2 g/kg IP), MZ (5.0 mg/kg IP), or control solution coadministered with the D1 dopamine antagonist SCH-23390 (0.025 or 0.05 mg/kg IP), the mixed dopamine antagonist haloperidol (0.05 or 0.075 mg/kg IP), or vehicle. After the injections on days 1, 7, and 10, mice were assessed in activity cages at different time intervals. Repeated administration of MZ resulted in an enhancement of its locomotor activating effects, behavioral sensitization. Further, the combined EtOH+MZ treatment also resulted in sensitization to its locomotor effects. Moreover, the development of MZ and EtOH+MZ sensitization was attenuated by both SCH-23390 and haloperidol. These data demonstrate that following repeated MZ or EtOH+MZ exposure mice show locomotor sensitization through DA receptor stimulation. Also, these findings suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by such combination.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Etanol/farmacologia , Mazindol/farmacologia , Atividade Motora/efeitos dos fármacos , Receptores Dopaminérgicos/efeitos dos fármacos , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Haloperidol/farmacologia , Masculino , Camundongos , Estimulação QuímicaRESUMO
The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol (EtOH) and diethylpropion (DEP) we examined the locomotion-activating effects of these drugs given alone or in combination in mice. We also determined whether this response was affected by dopamine (DA) or opioid receptor antagonists. A total of 160 male Swiss mice weighing approximately 30 g were divided into groups of 8 animals per group. The animals were treated daily for 7 consecutive days with combined EtOH + DEP (1.2 g/kg and 5.0 mg/kg, ip), EtOH (1.2 g/kg, ip), DEP (5.0 mg/kg, ip) or the control solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/kg, ip), the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip), or vehicle. On days 1, 7 and 10 after the injections, mice were assessed in activity cages at different times (15, 30, 45 and 60 min) for 5 min. The acute combination of EtOH plus DEP induced a significantly higher increase in locomotor activity (day 1: 369.5 +/- 34.41) when compared to either drug alone (day 1: EtOH = 232.5 +/- 23.79 and DEP = 276.0 +/- 12.85) and to control solution (day 1: 153.12 +/- 7.64). However, the repeated administration of EtOH (day 7: 314.63 +/- 26.79 and day 10: 257.62 +/- 29.91) or DEP (day 7: 309.5 +/- 31.65 and day 10: 321.12 +/- 39. 24) alone or in combination (day 7: 459.75 +/- 41.28 and day 10: 427. 87 +/- 33.0) failed to induce a progressive increase in the locomotor response. These data demonstrate greater locomotion-activating effects of the EtOH + DEP combination, probably involving DA and/or opioid receptor stimulation, since the daily pretreatment with HAL (day 1: EtOH + DEP = 395.62 +/- 11.92 and EtOH + DEP + HAL = 371.5 +/- 6.76; day 7: EtOH + DEP = 502.5 +/- 42.27 and EtOH + DEP + HAL = 281.12 +/- 16.08; day 10: EtOH + DEP = 445.75 +/- 16.64 and EtOH + DEP + HAL = 376.75 +/- 16.4) and NAL (day 1: EtOH + DEP = 553.62 +/- 38.15 and EtOH + DEP + NAL = 445.12 +/- 55.67; day 7: EtOH + DEP = 617.5 +/- 38.89 and EtOH + DEP + NAL = 418.25 +/- 61.18; day 10: EtOH + DEP = 541.37 +/- 32.86 and EtOH + DEP + NAL = 427.12 +/- 51.6) reduced the locomotor response induced by combined administration of EtOH + DEP. These findings also suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by the combination.
Assuntos
Depressores do Apetite/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Dietilpropiona/farmacologia , Antagonistas de Dopamina/farmacologia , Etanol/farmacologia , Atividade Motora/efeitos dos fármacos , Antagonistas de Entorpecentes , Animais , Interações Medicamentosas , Haloperidol/farmacologia , Masculino , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
This study examined the effects of pre-exercise carbohydrate availability on the time to exhaustion for moderate and heavy exercise. Seven men participated in a randomized order in two diet and exercise regimens each lasting 3 days with a 1-week interval for washout. The tests were performed at 50% of the difference between the first (LT1) and second (LT2) lactate breakpoint for moderate exercise (below LT2) and at 25% of the difference between the maximal load and LT2 for heavy exercise (above LT2) until exhaustion. Forty-eight hours before each experimental session, subjects performed a 90-min cycling exercise followed by 5-min rest periods and a subsequent 1-min cycling bout at 125% VO2max/1-min rest periods until exhaustion to deplete muscle glycogen. A diet providing 10% (CHO(low)) or 65% (CHO(mod)) energy as carbohydrates was consumed for 2 days until the day of the experimental test. In the exercise below LT2, time to exhaustion did not differ between the CHO(mod) and the CHO(low) diets (57.22 +/- 24.24 vs 57.16 +/- 25.24 min). In the exercise above LT2, time to exhaustion decreased significantly from 23.16 +/- 8.76 min on the CHO(mod) diet to 18.30 +/- 5.86 min on the CHO(low) diet (P < 0.05). The rate of carbohydrate oxidation, respiratory exchange ratio and blood lactate concentration were reduced for CHO(low) only during exercise above LT2. These results suggest that muscle glycogen depletion followed by a period of a low carbohydrate diet impairs high-intensity exercise performance.
Assuntos
Metabolismo dos Carboidratos/fisiologia , Carboidratos da Dieta/metabolismo , Metabolismo Energético/fisiologia , Resistência Física/fisiologia , Esforço Físico/fisiologia , Adulto , Carboidratos da Dieta/administração & dosagem , Teste de Esforço/métodos , Humanos , Masculino , Fatores de TempoRESUMO
Combined anorectic-alcohol misuse is a prevalent problem in Brazil. In order to understand better the interactive effects of ethanol (EtOH) and mazindol (MZ), we examined the effects of EtOH (1.2 g/kg) and MZ (5.0 mg/kg) given alone or in combination, on mouse behaviour. The results indicate that EtOH plus MZ induces a significantly greater increase in locomotor activity of mice than either constituent alone. However, no such interactive effect was detected in the place preference and in the plus-maze test of anxiety. MZ given alone was found to increase the locomotor activity and to possess rewarding effects as measured in the place preference conditioning. At the dose selected, EtOH alone showed anxiolytic and rewarding effects. These results provide some evidence of increased behavioural effects in mice due to combinations of EtOH and MZ. These findings suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced by such combination.
RESUMO
This study examined the effects of pre-exercise carbohydrate availability on the time to exhaustion for moderate and heavy exercise. Seven men participated in a randomized order in two diet and exercise regimens each lasting 3 days with a 1-week interval for washout. The tests were performed at 50 percent of the difference between the first (LT1) and second (LT2) lactate breakpoint for moderate exercise (below LT2) and at 25 percent of the difference between the maximal load and LT2 for heavy exercise (above LT2) until exhaustion. Forty-eight hours before each experimental session, subjects performed a 90-min cycling exercise followed by 5-min rest periods and a subsequent 1-min cycling bout at 125 percent VO2max/1-min rest periods until exhaustion to deplete muscle glycogen. A diet providing 10 percent (CHOlow) or 65 percent (CHOmod) energy as carbohydrates was consumed for 2 days until the day of the experimental test. In the exercise below LT2, time to exhaustion did not differ between the CHOmod and the CHOlow diets (57.22 ± 24.24 vs 57.16 ± 25.24 min). In the exercise above LT2, time to exhaustion decreased significantly from 23.16 ± 8.76 min on the CHOmod diet to 18.30 ± 5.86 min on the CHOlow diet (P < 0.05). The rate of carbohydrate oxidation, respiratory exchange ratio and blood lactate concentration were reduced for CHOlow only during exercise above LT2. These results suggest that muscle glycogen depletion followed by a period of a low carbohydrate diet impairs high-intensity exercise performance.
Assuntos
Adulto , Humanos , Masculino , Metabolismo dos Carboidratos/fisiologia , Carboidratos da Dieta/metabolismo , Metabolismo Energético/fisiologia , Resistência Física/fisiologia , Esforço Físico/fisiologia , Carboidratos da Dieta/administração & dosagem , Teste de Esforço/métodos , Fatores de TempoRESUMO
The objective of the present investigation was to test the effects of benserazide/L-dopa treatment in a model of learning and memory deficits associated with early Parkinson's disease. Intra-nigral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused a lesion in the substantia nigra, compact part and a specific loss of dopamine (DA) and its metabolites in the striatum of rats and a memory impairment in the two-way active avoidance task. The administration of benserazide/L-dopa (50 and 200 mg/kg) to the MPTP-lesioned rats restored the striatal level of DA, but did not reverse the MPTP-induced learning and memory impairment. As this treatment caused a large increase of DA levels in extrastriatal brain regions of the MPTP-lesioned animals, this study suggests that benserazide/L-dopa therapy was not effective in improving the observed learning impairment because this treatment appears to tilt the balance between DA levels in the striatum and in the extrastriatal regions, such as frontal cortex and limbic structures, resulting in a cognitive deficit.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Antiparkinsonianos/uso terapêutico , Corpo Estriado/metabolismo , Dopaminérgicos , Dopamina/metabolismo , Levodopa/uso terapêutico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Benserazida/farmacologia , Monoaminas Biogênicas/metabolismo , Química Encefálica/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Masculino , Transtornos da Memória/patologia , Ratos , Ratos Wistar , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The widespread consumption of anorectics and combined anorectic + alcohol misuse are problems in Brazil. In order to better understand the interactive effects of ethanol (EtOH) and diethylpropion (DEP) we examined the locomotion-activating effects of these drugs given alone or in combination in mice. We also determined whether this response was affected by dopamine (DA) or opioid receptor antagonists. A total of 160 male Swiss mice weighing approximately 30 g were divided into groups of 8 animals per group. The animals were treated daily for 7 consecutive days with combined EtOH + DEP (1.2 g/kg and 5.0 mg/kg, ip), EtOH (1.2 g/kg, ip), DEP (5.0 mg/kg, ip) or the control solution coadministered with the DA antagonist haloperidol (HAL, 0.075 mg/kg, ip), the opioid antagonist naloxone (NAL, 1.0 mg/kg, ip), or vehicle. On days 1, 7 and 10 after the injections, mice were assessed in activity cages at different times (15, 30, 45 and 60 min) for 5 min. The acute combination of EtOH plus DEP induced a significantly higher increase in locomotor activity (day 1: 369.5 + or - 34.41) when compared to either drug alone (day 1: EtOH = 232.5 + or - 23.79 and DEP = 276.0 + or - 12.85) and to control solution (day 1: 153.12 + or - 7.64). However, the repeated administration of EtOH (day 7: 314.63 + or - 26.79 and day 10: 257.62 + or - 29.91) or DEP (day 7: 309.5 + or - 31.65 and day 10: 321.12 + or - 39.24) alone or in combination (day 7: 459.75 + or - 41.28 and day 10: 427.87 + or - 33.0) failed to induce a progressive increase in the locomotor response. These data demonstrate greater locomotion-activating effects of the EtOH + DEP combination, probably involving DA and/or opioid receptor stimulation, since the daily pretreatment with HAL (day 1: EtOH + DEP = 395.62 + or - 11.92 and EtOH + DEP + HAL = 371.5 + or - 6.76; day 7: EtOH + DEP = 502.5 + or - 42.27 and EtOH + DEP + HAL = 281.12 + or - 16.08; day 10: EtOH + DEP = 445.75 + or - 16.64 and EtOH + DEP + HAL = 376.75 + or - 16.4) and NAL (day 1: EtOH + DEP = 553.62 + or - 38.15 and EtOH + DEP + NAL = 445.12 + or - 55.67; day 7: EtOH + DEP = 617.5 + or - 38.89 and EtOH + DEP + NAL = 418.25 + or - 61.18; day 10: EtOH + DEP = 541.37 + or - 32.86 and EtOH + DEP + NAL = 427.12 + or - 51.6) reduced the locomotor response induced by combined administration of EtOH + DEP. These findings also suggest that a major determinant of combined anorectic-alcohol misuse may be the increased stimulating effects produced...