RESUMEN
Midbrain dopamine (DA) neurons encode both reward- and movement-related events and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. In this study, we dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task and examining the influence on anticipatory licking before reward delivery. Inhibiting both ventral tegmental area and substantia nigra pars compacta DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations and suggest that directly generating movements is a comparatively less important function.
Asunto(s)
Dopamina/metabolismo , Neuronas Dopaminérgicas/fisiología , Mesencéfalo/fisiología , Movimiento/fisiología , Recompensa , Animales , Conducta Animal/fisiología , Condicionamiento Clásico , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
The Western diet has been associated with prostate cancer incidence as well as risk of disease progression after treatment. Conversely, plant-based diets have been associated with decreased risks. A pilot clinical trial of a 6-month dietary change and stress reduction intervention for asymptomatic, hormonally untreated patients experiencing a consistently rising PSA level, the first sign of recurrence of prostate cancer after surgery or radiation therapy, was conducted to investigate the level of intake of plant-based foods and the relationship between intake and the change in the rate of PSA rise. A pre-post design was employed in which each patient served as his own control. In this multifaceted intervention, patients and their spouses were encouraged to adopt and maintain a plant-based diet. The prestudy rate of PSA rise (from the time of posttreatment recurrence to the start of the study) was ascertained by review of patients' medical records. Dietary assessments were performed and prostate-specific antigen (PSA) levels ascertained at baseline, prior to the start of intervention, and at 3 and 6 months. Changes in numbers of servings of plant-based food groups were calculated and compared with rates of PSA rise over the corresponding time intervals. Median intake of whole grains increased from 1.7 servings/d at baseline to 6.9 and 5.0 servings/d at 3 and 6 months, respectively. Median intake of vegetables increased from 2.8 servings/d at baseline to 5.0 and 4.8 servings/d at 3 and 6 months, respectively. The rate of PSA rise decreased when comparing the prestudy period (0.059) to the period from 0 to 3 months (-0.002, P < .01) and increased slightly, though not significantly, when comparing the period from 0 to 3 months to the period from 3 to 6 months (0.029, P = .4316). These results provide preliminary evidence that adoption of a plant-based diet is possible to achieve as well as to maintain for several months in patients with recurrent prostate cancer. Changes in the rate of rise in PSA, an indicator of disease progression, were in the opposite direction as changes in the intake of plant-based food groups, raising the provocative possibility that PSA may have inversely tracked intake of these foods and suggesting that adoption of a plant-based diet may have therapeutic potential in the management of this condition.
Asunto(s)
Dieta Vegetariana , Conducta Alimentaria , Neoplasias de la Próstata/dietoterapia , Neoplasias de la Próstata/patología , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Resultado del TratamientoRESUMEN
A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic. While hormonal therapy may slightly extend survival in a minority of patients, it is not curative and produces side effects including hot flashes, decreased libido, and loss of bone mass. Alternatively, dietary modification may offer an important tool for clinical management. Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment. Conversely, many elements of plant-based diets have been associated with reduced risk of progression. However, dietary modification can be stressful and difficult to implement. We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet, reinforced by stress management training, could attenuate the rate of further PSA rise. Urologists at the University of California, San Diego, and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer. A pre-post design was employed in which each patient served as his own control. Rates of PSA rise were ascertained for each patient for the following periods: from the time of posttreatment recurrence up to the start of the study (prestudy) and from the time immediately preceding the intervention (baseline) to the end of the intervention (0-6 months). There was a significant decrease in the rate of PSA rise from prestudy to 0 to 6 months (P < .01). Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study. Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times. Median PSA doubling time increased from 11.9 months (prestudy) to 112.3 months (intervention). These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer.