Miguel Navarro | Universitas Pelita Harapan (original) (raw)

Papers by Miguel Navarro

Recent studies suggest that the endocannabinoid system modulates feeding. Despite the existence o... more Recent studies suggest that the endocannabinoid system modulates feeding. Despite the existence of central mechanisms for the regulation of food intake by endocannabinoids, evidence indicates that peripheral mechanisms may also exist. To test this hypothesis, we investigated (1) the effects of feeding on intestinal anandamide accumulation; (2) the effects of central (intracerebroventricular) and peripheral (intraperitoneal) administration of the endocannabinoid agonist anandamide, the synthetic cannabinoid agonist R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate (WIN55,212-2), and the CB1-selective antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A) on food intake in rats; and (3) the effects of sensory deafferentation on the modulation of feeding by cannabinoids. Food deprivation produced a sevenfold increase in anandamide content in the small intestine but not in the brain or stomach. Refeeding normalized intestinal anandamide levels. Peripheral but not central administration of anandamide or WIN55,212-2 promoted hyperphagia in partially satiated rats. Similarly, peripheral but not central administration of SR141716A reduced food intake. Capsaicin deafferentation abolished the peripheral effects of both cannabinoid agonists and antagonists, suggesting that these agents modulate food intake by acting on CB1 receptors located on capsaicin-sensitive sensory terminals. Oleoylethanolamide, a noncannabinoid fatty ethanolamide that acts peripherally, prevented hyperphagia induced by the endogenous cannabinoid anandamide. Pretreatment with SR141716A enhanced the inhibition of feeding induced by intraperitoneal administration of oleoylethanolamide. The results reveal an unexpected role for peripheral CB1 receptors in the regulation of feeding.

European Journal of Pharmacology, 1995

The present study investigated the effects of systemic administration of the putative dopamine D ... more The present study investigated the effects of systemic administration of the putative dopamine D 3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on the acquisition and expression of morphine-induced place preference in male Wistar rats. Using a a 3-day schedule of conditioning it was found that 7-OH-DPAT in a broad dose range (0.01, 0.25 and 5.0 mg/kg) did not produce significant place preference. However, the administration of either 0.25 or 5.0 mg/kg of 7-OH-DPAT 15 min prior to the exposure to morphine (1 mg/kg) prevented the acquisition of a morphine place preference, whereas the 0.01 mg/kg dose of the dopamine receptor agonist was uneffective. In addition, when 7-OH-DPAT was acutely administered 15 min prior to the testing session of an already established morphine place preference, the 0.01 mg/kg dose prevented the expression of this conditioned response. This effect was not observed with either 0.25 and 5.0 mg/kg doses of this dopamine D 3 receptor agonist. It was suggested that the different dose related effects of 7-OH-DPAT on the acquisition and expression of morphine place preference might be related to the intrinsic ability of this agonist for interacting with pre-and postsynaptic dopamine D 3 receptors located in limbic projecting areas of the mesencephalic dopamine system, although involvement of dopamine D 2 receptors cannot be excluded. The pattern of effects seen with 7-OH-DPAT suggests that it may be useful for treating opiate dependence and craving.

The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in... more The endogenous cannabinoid system is an ubiquitous lipid signalling system that appeared early in evolution and which has important regulatory functions throughout the body in all vertebrates. The main endocannabinoids (endogenous cannabis-like substances) are small molecules derived from arachidonic acid, anandamide (arachidonoylethanolamide) and 2-arachidonoylglycerol. They bind to a family of G-protein-coupled receptors, of which the cannabinoid CB 1 receptor is densely distributed in areas of the brain related to motor control, cognition, emotional responses, motivated behaviour and homeostasis. Outside the brain, the endocannabinoid system is one of the crucial modulators of the autonomic nervous system, the immune system and microcirculation. Endocannabinoids are released upon demand from lipid precursors in a receptor-dependent manner and serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of postsynaptic transmission, interacting with other neurotransmitters, including dopamine. Endocannabinoids are transported into cells by a specific uptake system and degraded by two well-characterized enzymes, the fatty acid amide hydrolase and the monoacylglycerol lipase. Recent pharmacological advances have led to the synthesis of cannabinoid receptor agonists and antagonists, anandamide uptake blockers and potent, selective inhibitors of endocannabinoid degradation. These new tools have enabled the study of the physiological roles played by the endocannabinoids and have opened up new strategies in the treatment of pain, obesity, neurological diseases including multiple sclerosis, emotional disturbances such as anxiety and other psychiatric disorders including drug addiction. Recent advances have specifically linked the endogenous cannabinoid system to alcoholism, and cannabinoid receptor antagonism now emerges as a promising therapeutic alternative for alcohol dependence and relapse.

European Journal of Pharmacology, 1999

Clinical and basic research studies have linked cannabinoid consumption to the onset of psychosis... more Clinical and basic research studies have linked cannabinoid consumption to the onset of psychosis, specially schizophrenia. In the present study we have evaluated the effects of the natural psychoactive constituent of Cannabis (-)-delta9-tetrahydrocannabinol on the acute actions of the psychostimulant, D-amphetamine, on behaviour displayed by male rats on a hole-board, a proposed animal model of amphetamine-induced psychosis. Cannabinoid-amphetamine interactions were studied (1) 30 min after acute injection of (-)-delta9-tetrahydrocannabinol (0.1 or 6.4 mg/kg, i.p.); (2) 30 min after the last injection of 14-daily treatment with (-)-delta9-tetrahydrocannabinol (0.1 or 6.4 mg/kg) and 3) 24 h after the last injection of 14-daily treatment with (-)-delta9-tetrahydrocannabinol (6.4 mg/kg). Acute cannabinoid exposure antagonized the amphetamine-induced dose-dependent increase in locomotion, exploration and the decrease in inactivity. Chronic treatment with (-)-delta9-tetrahydrocannabinol resulted in tolerance to this antagonistic effect on locomotion and inactivity but not on exploration, and potentiated amphetamine-induced stereotypies. Lastly, 24 h of withdrawal after 14 days of cannabinoid treatment resulted in sensitization to the effects of D-amphetamine on locomotion, exploration and stereotypies. Since (-)-delta9-tetrahydrocannabinol is a cannabinoid CB1 receptor agonist, densely present in limbic and basal ganglia circuits, and since amphetamine enhances monoaminergic inputs (i.e., dopamine, serotonin) in these brain areas, the present data support the hypothesis of a role for the cannabinoid CB1 receptor as a regulatory mechanism of monoaminergic neuron-mediated psychomotor activation. These findings may be relevant for the understanding of both cannabinoid-monoamines interactions and Cannabis-associated psychosis.

Metabolism-clinical and Experimental, 2000

Neuroreport, 1998

Recent reports have provided evidence of a link between the endogenous brain cannabinoid system a... more Recent reports have provided evidence of a link between the endogenous brain cannabinoid system and the endogenous central opioid systems. Here we report that the selective CB1 receptor antagonist SR 141716A induced behavioral and endocrine alterations associated with opiate withdrawal in morphine-dependent animals in a dose-dependent manner and that naloxone induced an opiate withdrawal syndrome in animals made cannabinoid-dependent by repeated administration of the potent cannabinoid agonist HU-210. Additionally CB1 and mu-opioid receptor mRNAs were co-localized in brain areas relevant for opiate withdrawal such as the nucleus accumbens, septum, dorsal striatum, the central amygdaloid nucleus and the habenular complex. These results suggest that CB1 cannabinoid receptors may play a role in the neuroadaptive processes associated with opiate dependence, and they lend further support for the hypothesis of a potential role of cannabinoid receptors in the neurobiological changes that culminate in drug addiction.

Neuroreport, 1997

ANIMAL models have revealed that psychoactive cannabinoids induce both anxiolytic and anxiety-lik... more ANIMAL models have revealed that psychoactive cannabinoids induce both anxiolytic and anxiety-like reactions which are dose-and context-dependent. In the present study we examined the acute actions of the CB 1 cannabinoid receptor antagonist SR 141716A in both the defensive withdrawal test and the elevated plus-maze in rats. Acute administration of SR 141716A (0.1, 1 and 3 mg kg -1 ) induced defensive responses in both anxiety tests, at a dose of 3 mg kg -1 . This dose had no effect on horizontal locomotor activity and did not activate the hypothalamus-pituitary-adrenal axis, although several cannabinoid withdrawal-like behavioural symptoms were observed. These results demonstrate that blockade of the endogenous cannabinoid tone might induce anxiety-like responses in rats.

Neurobiology of Disease, 1998

One of the prominent pharmacological features of drugs acting at the brain cannabinoid receptor (... more One of the prominent pharmacological features of drugs acting at the brain cannabinoid receptor (CB1) is the induction of alterations in motor behavior. Catalepsy, immobility, ataxia, or the impairment of complex behavioral acts are observed after acute administration of either natural and synthetic cannabinoid receptor agonists or the endogenous CB1 ligand anandamide. The dense presence of CB1 receptors in the cerebellum and in the basal ganglia, especially at the outflow nuclei (substantia nigra and the internal segment of the globus pallidus), supports the existence of an endogenous cannabinoid system regulating motor activity. In the basal ganglia, the functionality of the anandamide-CB1 system is poorly understood. Dual effects are often observed after the administration of CB1 ligands in animal models of pharmacological manipulation of basal ganglia transmitter systems, indicating that the activity of the anandamide-CB1 system depends on the ongoing activation of the different elements of the basal ganglia. This finding is in agreement with the proposed activity-dependent release of anandamide from a plasmalemma precursor. Additionally, a potential state-dependent bidirectional coupling of the CB1 receptor to the adenylate cyclase transduction system has also been described. From this perspective, the endogenous cannabinoid system can be proposed as a local regulator of neurotransmission processes within the basal ganglia. This system may serve as a counterregulatory homeostatic mechanism preserving the functional role of basal ganglia circuits in coding the serial order of events that constitute movement.

Annals of Oncology, 2008

Background: To demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-f... more Background: To demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX-4) as second-line therapy in patients with metastatic colorectal cancer after prior irinotecan-based chemotherapy.

Lancet, 2000

Background Irinotecan is active against colorectal cancer in patients whose disease is refractory... more Background Irinotecan is active against colorectal cancer in patients whose disease is refractory to fluorouracil. We investigated the efficacy of these two agents combined for first-line treatment of metastatic colorectal cancer.

Las tendencias actuales respecto al aprendizaje, señalan una fuerte orientación hacia el aprendiz... more Las tendencias actuales respecto al aprendizaje, señalan una fuerte orientación hacia el aprendizaje centrado en el alumno; precisamente, el que nuestra actual época sea conocida como "sociedad del conocimiento" obliga a desplegar esfuerzos al nivel de las políticas educativas para promover esta línea, lo anterior es reconocido por Chocarro, et al y por , al señalarse que dicha sociedad del conocimiento demanda específicamente de un aprendizaje autorregulado de parte de los aprendices de nuestro tiempo, de ahí la especial importancia a estudiar tanto el paradigma de la enseñanza centrado en el aprendizaje del alumno, como el proceso de autorregulación de los estudiantes (Ogawa, 2011).

Drafts by Miguel Navarro

Resumen En el presente trabajo se abordó como objeto de investigación, a los saberes docentes de ... more Resumen En el presente trabajo se abordó como objeto de investigación, a los saberes docentes de los profesores memorables desde la perspectiva de los estudiantes; se utilizó el método de investigación narrativa; por lo cual se categorizaron 28 textos escritos por estudiantes de la Licenciatura en Pedagogía de la Universidad Veracruzana. Los objetivos se orientaron a: categorizar los significados de los saberes docentes, explicar aquellos saberes docentes que dejaron huella en la vida de los aprendices, describir los saberes docentes del ámbito técnico profesional y distinguir aquellas categorizaciones que implicaban a los malos profesores. Los resultados muestran a 8 categorías que responden a los objetivos de la indagación, las cuales son: saber didáctico, saber humano-paciencia-comprensión, saber explicar-don de la enseñanza, saber docente estrategias, saberes docentes específicos de profesores memorables, saber planear-evaluar, saber rigor-pulcritud-formato y saber buena actitud del maestro.