Dopamine, Norepinephrine and Serotonin Participate Differently in Methylphenidate Action in Concomitant Behavioral and Ventral Tegmental Area, Locus Coeruleus and Dorsal Raphe Neuronal Study in Young Rats.

Methylphenidate (MPD), known as Ritalin, is a psychostimulant used to treat children, adults, and the elderly. MPD exerts its effects through increasing concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the synaptic cleft. Concomitant behavioral and neuronal recording from the ventral tegmental area (VTA), locus coeruleus (LC), and from the dorsal raphe (DR) nucleus, which are the sources of DA, NE, and 5-HT to the mesocorticolimbic circuit, were investigated following acute and repetitive (chronic) saline, 0.6, 2.5, or 10.0 mg/kg MPD. Animals received daily saline or MPD administration on experimental days 1 to 6 (ED1-6), followed by a 3-day washout period and MPD rechallenge on ED10. Each chronic MPD dose elicits behavioral sensitization in some animals while inducing behavioral tolerance in others. The uniqueness of this study is in the evaluation of neuronal activity based on the behavioral response to chronic MPD. Neuronal excitation was observed mainly in brain areas of animals exhibiting behavioral sensitization, while neuronal attenuation following chronic MPD was observed in animals expressing behavioral tolerance. Different ratios of excitatory/inhibitory neuronal responses were obtained from the VTA, LC, or DR following chronic MPD. Thus, each brain area responds differently to each MPD dose used, suggesting that DA, NE, and 5-HT in the VTA, LC, and DR exert different effects.

Caudate nucleus neurons participate in methylphenidate function: Behavioral and neuronal recordings from freely behaving adolescent rats.

Methylphenidate (MPD) is the most commonly prescribed psychostimulant for the treatment of attention-deficit hyperactivity disorder (ADHD). MPD acts on brain structures of the reward/motivation system, including the caudate nucleus (CN). The objective of this study was to investigate the acute and chronic dose response effects of MPD on CN neurons in freely behaving adolescent rats. Semi-microelectrodes were implanted into the CN of one hundred and sixty-three adolescent male Sprague-Dawley rats. On experimental day one (ED1), each rat was injected with 0.8 ml saline followed by an injection of MPD (0.6, 2.5, or 10.0 mg/kg). Behavioral and neuronal recordings of 60 min followed each injection. Throughout ED2-6, each rat remained in its home cage and received daily injections of a specific dose of MPD. ED7-9 consisted of a three-day washout period during which no injections were given. On the last day (ED10), each rat was returned to the testing chamber in its home cage and an identical protocol was performed as on ED1. The same repetitive (i.e. chronic) dose of MPD elicited behavioral sensitization in some animals and behavioral tolerance in others. After chronic MPD exposure, CN units recorded from rats expressing behavioral sensitization responded mainly with increased neuronal firing rates. Conversely, rats expressing behavioral tolerance responded mainly with decreased neuronal firing rates. These findings suggest a direct correlation between the behavioral and CN neurophysiological response to chronic MPD in adolescent animals.

Methylphenidate modulates dorsal raphe neuronal activity: Behavioral and neuronal recordings from adolescent rats.

Methylphenidate (MPD) is a widely prescribed psychostimulants used for the treatment of attention deficit hyperactive disorder (ADHD). Unlike the psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on the serotonin transporter, however there is evidence suggesting that the therapeutic effects of MPD may be mediated in part by alterations in serotonin transmission. This study aimed to investigate the role of the dorsal raphe (DR) nucleus, one of the major sources of serotonergic innervation in the mammalian brain, in the response to MPD exposure. Freely behaving adolescent rats previously implanted bilaterally with permanent electrodes were used. An open field assay and a wireless neuronal recording system were used to concomitantly record behavioral and DR electrophysiological activity following acute and chronic MPD exposure. Four groups were used: one control (saline) and three experimental groups treated with 0.6, 2.5, and 10.0mg/kg MPD respectively. Animals received daily MPD or saline injections on experimental days 1-6, followed by 3 washout days and MPD rechallenge dose on experimental day (ED)10. The same chronic dose of MPD resulted in either behavioral sensitization or tolerance, and we found that neuronal activity recorded from the DR neuronal units of rats expressing behavioral sensitization to chronic MPD exposure responded significantly differently to MPD rechallenge on ED10 compared to the DR unit activity recorded from animals that expressed behavioral tolerance. This correlation between behavioral response and DR neuronal activity following chronic MPD exposure provides evidence that the DR is involved in the acute effects as well as the chronic effects of MPD in adolescent rats.

Behavioral and neuronal recording of the nucleus accumbens in adolescent rats following acute and repetitive exposure to methylphenidate.

The nucleus accumbens (NAc) has been shown to play a key role in the brain's response to methylphenidate (MPD). The present study focuses on neuronal recording from this structure. The study postulates that repetitive exposure to the same dose of MPD will elicit in some rats behavioral sensitization and in others tolerance. Furthermore, the study postulates that NAc neuronal activity recorded from animals expressing behavioral tolerance after repetitive MPD exposure will be significantly different from NAc neuronal activity recorded from animals expressing behavioral sensitization after repetitive MPD exposure at doses of 0.6, 2.5, 5.0, and 10.0 mg/kg. To test this, behavioral and neuronal activity was recorded concomitantly from the NAc of freely behaving adolescent rats (postnatal day 40) before and after acute and repetitive administration of four different MPD doses. Comparing the acute MPD effect to the repetitive MPD effect revealed that the acute response to MPD exhibited dose-response characteristics: an increase in behavioral activity correlated with increasing MPD doses. On the other hand, following repetitive MPD exposure, some animals exhibited attenuated behavior (tolerance), while others exhibited further increases in the recorded behavior (sensitization). Moreover, the neuronal activity following repetitive MPD exposure recorded in animals exhibiting behavioral sensitization was significantly different from neuronal activity recorded in animals exhibiting behavioral tolerance. This implies that when studying the effects of repetitive MPD administration on adolescent rats, it is advisable to simultaneously record both neuronal and behavioral activity and to evaluate all data based on the animals' behavioral response to the repetitive MPD exposure.

Alcohol usage and abrupt cessation modulate diurnal activity.

Alcohol has many effects throughout the body. The effect on circadian rhythms and the correlation of these effects to withdrawal effects of alcohol present interesting findings. By measuring 3 planes of activity of female Sprague-Dawley rats during alcohol usage and continuing study through the first 2 days following withdrawal of alcohol allow for the observation of a drastic modulation of the circadian pattern of activity.

Análisis fisiológico de la acción fibrinolítica de bromelinas sobre una trombosis experimental / Physiological analysis of fibrinolytic action of bromelain on an experimental thrombosis

Se evaluó la acción fibrinolítica de las bromelinas (BRO) sobre una trombosis experimental inducida por destrucción del endotelio vascular en una porción de la arteria femoral de perros (n=10). Se hicieron registros de: resistencia galvánica de la piel (RGP), temperatura subcutánea proximal (TP) y distal (TD) y flujo sanguíneo distal al sitio de lesión, frecuencia cardíaca y de ventilación y presión arterial (PA). Solo a 5 de los sujetos se les administró una dosis BRO (10mg/kg, vía I.V.) 48 horas después de inducir la trombosis. Al final, se realizó el análisis histológico del ramo arterial lesionado, el cual comprendió: extensión y penetración de la inflamación, infiltración hemorrágica y grado de trombosis. El análisis computarizado de los registros poligráficos mostró gran variabilidad entre los sujetos desde los períodos controles. Sin embargo, el análisis individual mostró una acción del tratamiento, especialmente en las variables RGP, flujo sanguíneo, TP, TD, y PA en la mayoría de los animales. En todos los sujetos se observó necrosis del endotelio, ruptura focal de la lámina elástica interna y diverso grado de trombosis. Los resultados apoyan una acción fibrinolítica de las BRO sugiriendo otros estudios con dosis mayores o repetidas que justifiquen su utilización en el tratamiento de enfermedades tromboembólicas