RESUMEN
PURPOSE: To better understand the behavioral effects of pallidotomy as a treatment for a range of movement disorders, including Parkinson's disease, chorea, and ballismus. In some cases, pallidotomy increases movement whereas in others it decreases unwanted motor behavior. METHOD: The present study investigated the effects of unilateral pallidotomy in rats with an otherwise healthy nervous system. Pallidotomized and sham lesion rats were evaluated on a battery of tests that measure sensorimotor behavior. RESULTS: Compared to sham lesion controls, pallidotomized rats showed motor deficits (forelimb placing; bracing) and excesses (locomotor behavior) as well as sensorimotor asymmetries (ipsilateral adhesive patch bias; increased contralateral foot faults). CONCLUSION: Motor deficits observed after pallidotomy were similar to those reported in previous research from this and other laboratories following damage to the nigrostriatal pathway or sensorimotor cortex. Motor excesses after pallidotomy are consistent with current theories of globus pallidus function. Taken together, these data suggest hypokinetic effects of pallidotomy may be related to fibers of passage (i.e. internal capsule), while hyperkinetic effects may be related to damage of pallidal cell bodies. These data may have important clinical implications because they suggest that regardless of the state of existing pathology, pallidotomy may create unwanted behavioral side effects.
Asunto(s)
Lateralidad Funcional/fisiología , Globo Pálido/fisiopatología , Globo Pálido/cirugía , Trastornos del Movimiento/fisiopatología , Movimiento/fisiología , Análisis de Varianza , Animales , Conducta Animal , Miembro Anterior/fisiopatología , Masculino , Trastornos del Movimiento/etiología , Desempeño Psicomotor/fisiología , Ratas , Ratas Long-Evans , Factores de Tiempo , Vibrisas/fisiologíaRESUMEN
Magnesium has been shown to be involved with the processes associated with brain injury and its use in animal models of brain injury has received considerable attention. The present paper reviews the use of MgCl2 therapy to facilitate behavioral recovery and to reduce subcortical degeneration in an electrolytic lesion model of cortical injury in the rat. Several studies were performed which compared the effectiveness of MgCl2 to other established neuroprotective agents, examined the preoperative administration of MgCl2, and examined the effectiveness of MgCl2 in a lesion model that produces chronic behavioral impairments. The results from these studies indicate that MgCl2 therapy is effective in facilitating recovery of function and limiting subcortical degeneration, is as effective as other neuroprotective agents, and can induce recovery of function in a chronic lesion model. These results suggest that MgCl2 therapy is effective in facilitating recovery of function in an electrolytic lesion model of cortical injury.
Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Corteza Cerebral/metabolismo , Cloruro de Magnesio/uso terapéutico , Magnesio/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Humanos , Ratas , Factores de TiempoRESUMEN
Previous studies have utilized a lesion model of cortical injury that produces transient behavioral impairments to investigate the recovery of function process. To better understand the recovery process, it would be beneficial to use a lesion model that produces more severe, enduring, behavioral impairments. The purpose of experiment 1 was to validate whether large lesions of the sensorimotor cortex (SMC), which included the rostral forelimb and caudal forelimb regions, produced enduring behavioral deficits. Rats were given large unilateral electrolytic lesions of the SMC, administered either the N-methyl-D-aspartate (NMDA) antagonist, MK-801 or saline 16 h after injury, and tested on a battery of behavioral tests. Enduring behavioral deficits were observed, for at least 6 months, on two tests of forelimb placing while transient deficits were observed on the foot-fault and somatosensory neutralization tests. Administration of MK-801 facilitated recovery on the somatosensory neutralization test; however, it did not induce recovery on either forelimb placing test. A second experiment was performed to determine if earlier administration of MK-801, the NMDA antagonist magnesium chloride (MgCl(2)), or the anti-oxidant N-tert-butyl-alpha-phenylnitrone (PBN) could induce behavioral recovery in this chronic model. Treatment with these drugs induced behavioral recovery on the forelimb placing tests, whereas, the saline-treated rats did not show any signs of behavioral recovery for at least 3 months. Anatomical analysis of the striatum showed that MK-801 and MgCl(2) but not PBN reduced the extent of lesion-induced striatal atrophy. These results suggest that administration of MK-801, MgCl(2), or PBN shortly after cortical injury can induce recovery of function when recovery is otherwise not expected in un-treated rats.
Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Corteza Motora/efectos de los fármacos , Corteza Motora/lesiones , Degeneración Nerviosa/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Animales , Antioxidantes/farmacología , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Óxidos N-Cíclicos , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Miembro Anterior/efectos de los fármacos , Miembro Anterior/inervación , Miembro Anterior/fisiopatología , Cojera Animal/tratamiento farmacológico , Cojera Animal/patología , Cojera Animal/fisiopatología , Cloruro de Magnesio/farmacología , Masculino , Actividad Motora/fisiología , Corteza Motora/fisiopatología , Degeneración Nerviosa/patología , Degeneración Nerviosa/fisiopatología , Óxidos de Nitrógeno/farmacología , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Tacto/efectos de los fármacos , Tacto/fisiología , Vibrisas/efectos de los fármacos , Vibrisas/inervación , Vibrisas/fisiologíaRESUMEN
Following brain injury, there is a reduction of intra- and extracellular levels of magnesium (Mg++), which may contribute to the severity of the lesion-induced behavioral impairments. Injections of magnesium prior to or after brain injury attenuate these behavioral impairments. The present study extends these findings by manipulating the number of injections and the time period between the injections and the time of injury. Rats were given either two or five daily preoperative injections of MgCl2 (1 mmol/kg, i.p.), or saline (1 ml/kg, i.p.) with the final injection given 24 h prior to electrolytic lesions of the somatic sensorimotor cortex (SMC). Following SMC lesions the rats exhibited contralateral deficits in forelimb placing and locomotor placing. Rats treated with either two or five preoperative injections of MgCl2 showed a reduction in the initial magnitude of the contralateral deficits and an accelerated rate of recovery compared to saline-treated rats. In addition, analysis of striatal atrophy revealed that MgCl2 treatment prevented atrophy in the ipsilateral posterior striatum compared to rats treated with saline. These data suggest that preoperative injections of MgCl2 produce facilitation of sensorimotor recovery and reduce subcortical atrophy. Moreover, to observe the beneficial effects of MgCl2, the timing of injections need not be tied to the period immediately around the brain injury. The present data may indicate that daily supplements of magnesium may partially protect against some of the deleterious effects of brain injury.
Asunto(s)
Lesiones Encefálicas/fisiopatología , Corteza Cerebral/patología , Cloruro de Magnesio/farmacología , Actividad Motora/fisiología , Desempeño Psicomotor/fisiología , Corteza Somatosensorial/fisiopatología , Animales , Atrofia , Lesiones Encefálicas/patología , Corteza Cerebral/efectos de los fármacos , Esquema de Medicación , Miembro Anterior/inervación , Locomoción , Masculino , Actividad Motora/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Corteza Somatosensorial/efectos de los fármacos , Corteza Somatosensorial/patología , Factores de Tiempo , Vibrisas/inervaciónRESUMEN
This study investigated the relative contribution of amphetamine administration and task-specific practice during the period of drug action to recovery of forelimb-placing ability after unilateral electrolytic lesions of the sensorimotor cortex (SMC) in rats. Subjects were divided into groups receiving amphetamine plus postinjection forelimb-placing practice, amphetamine only, saline plus postinjection forelimb-placing practice, or saline only. The results revealed that groups of subjects receiving either amphetamine, postinjection practice, or a combination of these treatments exhibited the greatest enhancement of rates of vibrissae-evoked forelimb-placing recovery. These data suggest that these treatments can have an enduring beneficial effect on vibrissae-evoked forelimb-placing recovery without any immediate restorative effect on forelimb-placing ability. The recovery patterns and experimental evidence (see Feeney and Sutton, 1988; Chaouloff, 1989) suggest that the beneficial effect of the two therapies may be mediated by catecholamine release.
Asunto(s)
Anfetamina/farmacología , Lesiones Encefálicas/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/farmacología , Miembro Anterior/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Wistar , Análisis y Desempeño de TareasRESUMEN
Following brain injury there is an excessive release of glutamate, a reduction in levels of cellular Mg+ +, and the generation of oxygen free radicals. These processes may contribute to the severity of the behavioral impairments seen following brain injury by leading to secondary neuronal degeneration. The present experiment investigates the relative effects of three drugs (MK-801, an NMDA antagonist; magnesium chloride, an NMDA antagonist; and N-tert-butyl-α-phenylnitrone (PBN), an anti-oxidant and free radical scavenger) which disrupt different aspects of the pathophysiological process, in reducing these impairments. Direct comparisons of these drugs may determine if one treatment is more effective than another, or if one is detrimental. In addition, the effects of combination treatments including PBN and MK-801 or MgCl2 were examined. These combination treatment were aimed at the possibility of potentiating the beneficial effects observed after administration of these agents alone. Rats received unilateral electrolytic lesions of the somatic sensorimotor cortex followed by a regimen of MK-801 (1 mg/kg), MgCl2 (1 mmol/kg), PBN (100 mg/kg), MK-801 + PBN (1 mg/kg, 100 mg/kg), MgCl2 + PBN (1 mmol/kg, 100 mg/kg), or saline (1 ml/kg) beginning 15 min following injury. Rats were tested on several sensorimotor tasks (i.e. forelimb placing and foot-fault) for 43 days following the cortical lesions. Rats receiving any of the single or combination drug treatments showed a significant facilitation of recovery on the sensorimotor tasks compared to saline control rats. On one behavioral test (i.e. foot-fault) there was a significant further enhancement of the recovery by combination treatments compared to the single treatment groups. These data are consistent with the idea that excessive release of glutamate, reduction in Mg+ + levels, and free radical generation contribute to the severity of the behavioral impairments following cortical injury, and that arresting these processes results in a facilitation of behavioral recovery. Anatomical analysis showed that all drug treatments decreased the amount of atrophy seen in the ipsilateral striatum.
RESUMEN
The effects of amphetamine on the recovery of function following unilateral lesions of the rat somatic sensorimotor cortex (SMC) were examined. Rats with large SMC were tested on two measures of locomotor placing: the beam-walking test and the foot-fault test. Amphetamine produced an immediate and enduring facilitation of recovery on the beam-walking test. In contrast, the drug had no effect on the rats' ability to accurately place the forelimbs on the rungs of the elevated grid during locomotion on the foot-fault test. These data suggest that amphetamine may facilitate recovery when the requirements of the task produce a deficit in the initiation of locomotion but not when the animal is required to use somatosensory and proprioceptive cues to guide performance on the task. A second group of rats with smaller SMC lesions was evaluated with tactile-placing tests and the bilateral-tactile stimulation task. The forelimb placing reaction is elicited by unilateral tactile stimulation of the vibrissae or forelimb, whereas the ipsilateral asymmetry observed on the bilateral-tactile stimulation test has been interpreted as an impairment in processing stimuli presented on both sides of the body. On two measures of forelimb placing amphetamine produced a facilitation of recovery, but restoration of function was not observed during the period of drug intoxication. In contrast, amphetamine had no effect on recovery of function on the bilateral-tactile stimulation test. Taken together, these data suggest that the behavioral requirements of the task are an important factor in determining the facilitatory effects of amphetamine on recovery of function.
Asunto(s)
Corteza Cerebral/lesiones , Dextroanfetamina/farmacología , Desempeño Psicomotor/fisiología , Animales , Estimulantes del Sistema Nervioso Central/farmacología , Corteza Cerebral/patología , Señales (Psicología) , Relación Dosis-Respuesta a Droga , Miembro Anterior/inervación , Miembro Anterior/fisiología , Masculino , Equilibrio Postural/efectos de los fármacos , Propiocepción/efectos de los fármacos , Propiocepción/fisiología , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Tacto/fisiología , Vibrisas/fisiologíaRESUMEN
Following brain injury there is an excessive release of excitatory neurotransmitters that may lead to secondary cell death. Although much research has focused on glutamate-NMDA receptor interactions, acetylcholine-muscarinic receptor interactions may also prove to be important for an understanding of the pathophysiological events that lead to secondary degeneration after brain damage. Previous experiments have shown that the muscarinic receptor antagonist scopolamine facilitates recovery from very transient (1 h-10 days) behavioral deficits after fluid percussion injury. The present study extends these findings by investigating whether scopolamine can facilitate recovery from the more enduring behavioral deficits (14-60 days) that follow electrolytic lesions of the rat somatic sensorimotor cortex (SMC). Rats received unilateral lesions of the SMC and a regimen of scopolamine (1 mg/kg) or saline beginning 15 min after surgery. Following SMC lesions rats exhibited an impairment in placing the forelimb contralateral to the lesion as well as an ipsilateral somatosensory asymmetry on a bilateral tactile stimulation test. Rats treated with scopolamine showed a reduction in the initial magnitude of the contralateral placing deficit and an accelerated rate of recovery compared with saline-treated control rats. In contrast, scopolamine had no effect on recovery from the ipsilateral somatosensory asymmetry. These data are consistent with the idea that muscarinic receptor stimulation plays a role in the production of secondary brain damage, that blockade of this receptor leads to a facilitation of recovery on some behavioral tasks, and that electrolytic lesions may trigger some of the same posttraumatic events described in other models of neural trauma.
RESUMEN
Following unilateral lesions of the anteromedial cortex (AMC) or the caudal forelimb representation (CFL), rats prefer to remove an adhesive patch placed on the forelimb ipsilateral to the lesion before removing a simultaneously applied contralateral patch (i.e., ipsilateral asymmetry). The present experiment was designed to investigate the possibility that attention has some role in these asymmetries. Specifically, the researchers investigated whether a contralateral tactile cue presented before the simultaneous presentation of bilateral tactile stimuli would neutralize the ipsilateral asymmetry. In rats with AMC lesions, the contralateral cue neutralized the ipsilateral bias, whereas the cue had no effect on rats with CFL lesions. These data suggest that the ipsilateral bias observed in AMC-damaged rats may reflect an impairment in attention.
Asunto(s)
Atención/fisiología , Corteza Cerebral/fisiología , Dominancia Cerebral/fisiología , Extinción Psicológica/fisiología , Tacto/fisiología , Animales , Señales (Psicología) , Miembro Anterior/inervación , Lateralidad Funcional/fisiología , Masculino , Mecanorreceptores/fisiología , Ratas , Ratas Wistar , Vibrisas/inervaciónRESUMEN
Experiments involving the heterotopic transplantation of neocortex during development have indicated that the efferent connections maintained by the transplant as well as other organizational features are appropriate to the transplant's regional locale within the host cortex, rather than to its site of origin within the donor cortex. These findings would seem to be consistent with the idea that developing cortical neurons lack any rigid regional specification. To examine this further, we made lesions in the rostral cortex of newborn rats and placed pieces of either rostral or occipital fetal cortex into the lesion site. Additional cases with similar lesions, but with no transplants, were also prepared. When the animals matured, behavioral testing was done to identify any residual deficits. Compared with lesioned animals that had received no transplants, animals with homotopic transplants show a substantial sparing in certain forelimb placing and somatosensory tasks. In marked contrast, animals with heterotopic transplants did not show any sparing. Indeed, when placing reactions were elicited by vibrissal stimulation (vibrissae-->forelimb placing; extinction-placing) the animals with heterotopic transplants showed a greater impairment than the lesioned animals that received no transplants. These results indicate that while homotopic fetal cortical transplants may help ameliorate behavioral deficits that normally follow neonatal lesions of the rostral cortex, heterotopic transplants do not, and may in fact exacerbate the deficits, despite the fact that such heterotopic transplants have been shown to maintain projections that seemingly are appropriate to their locale.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trasplante de Tejido Fetal , Miembro Anterior/fisiopatología , Lóbulo Frontal/embriología , Lóbulo Frontal/cirugía , Tacto/fisiología , Animales , Encefalopatías/cirugía , Lóbulo Frontal/fisiopatología , Estimulación Física , Ratas , Ratas Endogámicas , Trasplante HeterotópicoRESUMEN
Previous reports have argued that single neurons in the ventral premotor cortex of rhesus monkeys (PMv, the ventrolateral part of Brodmann's area 6) typically show spatial response fields that are independent of gaze angle. We reinvestigated this issue for PMv and also explored the adjacent prearcuate cortex (PAv, areas 12 and 45). Two rhesus monkeys were operantly conditioned to press a switch and maintain fixation on a small visual stimulus (0.2 degree x 0.2 degree) while a second visual stimulus (1 degree x 1 degree or 2 degrees x 2 degrees) appeared at one of several possible locations on a video screen. When the second stimulus dimmed, after an unpredictable period of 0.4-1.2 s, the monkey had to quickly release the switch to receive liquid reinforcement. By presenting stimuli at fixed screen locations and varying the location of the fixation point, we could determine whether single neurons encode stimulus location in "absolute space" or any other coordinate system independent of gaze. For the vast majority of neurons in both PMv (90%) and PAv (94%), the apparent response to a stimulus at a given screen location varied significantly and dramatically with gaze angle. Thus, we found little evidence for gaze-independent activity in either PMv or PAv neurons. The present result in frontal cortex resembles that in posterior parietal cortex, where both retinal image location and eye position affect responsiveness to visual stimuli.
Asunto(s)
Corteza Cerebral/fisiología , Lóbulo Frontal/fisiología , Neuronas/fisiología , Visión Ocular/fisiología , Animales , Corteza Cerebral/citología , Electromiografía , Lóbulo Frontal/citología , Macaca mulatta , Masculino , Microelectrodos , Estimulación LuminosaRESUMEN
Histologic evidence suggests that drugs acting as noncompetitive antagonists at the N-methyl-D-aspartate receptor can have beneficial or pathologic effects on central nervous system neurons. In the present experiments we examined the effects of MK-801 on recovery of behavioral function after unilateral lesions in the rat somatic sensorimotor cortex. In the first experiment, rats with unilateral sensorimotor cortex lesions were given either MK-801 (1 mg/kg) or saline 12-16 hours after surgery. Additional injections were given on postoperative days 2, 4, and 6. Behavioral tests measured somatosensory asymmetries (i.e., bilateral tactile stimulation tests) and forelimb placing. After creation of sensorimotor cortex lesions, rats showed an ipsilateral somatosensory bias and an impairment in placing the contralateral forelimb. Rats treated with MK-801 recovered slightly faster than saline-treated animals as measured by a bilateral tactile stimulation test (p less than 0.05). In contrast, there was no significant difference between the groups in the recovery of forelimb placing. In a second experiment, rats with sensorimotor cortex lesions were treated with a single injection of MK-801 after behavioral recovery. Twenty hours after the MK-801 injection, rats with sensorimotor cortex lesions showed a reinstatement of the placing deficits. The impairment endured for at least 7 days after injection. These behavioral data support the idea that MK-801 can have either beneficial or detrimental effects when administered after brain damage.
Asunto(s)
Encefalopatías/fisiopatología , Maleato de Dizocilpina/uso terapéutico , Sistema Nervioso/fisiopatología , Corteza Somatosensorial/fisiopatología , Animales , Encefalopatías/tratamiento farmacológico , Maleato de Dizocilpina/farmacología , Miembro Anterior/fisiología , Masculino , Movimiento , Sistema Nervioso/efectos de los fármacos , Vías Nerviosas/fisiología , Estimulación Física , Ratas , Ratas Endogámicas , Corteza Somatosensorial/efectos de los fármacos , Vibrisas/fisiologíaRESUMEN
Following unilateral lesions of the somatic sensorimotor cortex (SMC) in neonatal, but not adult, rats, an aberrant ipsilateral corticospinal projection originates from the undamaged hemisphere (Hicks and D'Amato, 1970; Leong and Lund, 1973; Castro, 1975). We have evaluated the contribution of the hemisphere contralateral to a unilateral lesion of the SMC in the recovery of tactile forelimb-placing behavior. Neither adult-lesioned or neonatally lesioned animals show evidence for placing deficits with either forelimb when tested 30 or 42 d after the lesion. However, in adult-lesioned animals, a subsequent lesion of the undamaged SMC on postlesion day 42 produces placing deficits only with the forelimb contralateral to the second lesion, while such a second lesion in the neonatally lesioned rats results in placing deficits with both forelimbs. Anatomical observations in the animals used for behavioral analyses confirm previous reports of a substantial ipsilateral corticospinal projection in rats with unilateral SMC damage as neonates and demonstrate that many of these aberrant fibers recross the midline within the spinal cord to arborize extensively within the ipsilateral spinal gray. These findings indicate that, following unilateral SMC lesions in neonates, the contralateral hemisphere mediates some aspects of the recovery of forelimb placing. The aberrant ipsilateral corticospinal projection may provide the anatomical substrate through which the cortex effects this recovery.
Asunto(s)
Animales Recién Nacidos/fisiología , Conducta Animal/fisiología , Miembro Anterior/fisiología , Lateralidad Funcional , Actividad Motora/fisiología , Corteza Motora/fisiología , Animales , Corteza Cerebral/anatomía & histología , Corteza Motora/cirugía , Vías Nerviosas/anatomía & histología , Ratas , Ratas Endogámicas , Médula Espinal/anatomía & histología , TactoRESUMEN
The behavioural impairments and subsequent recovery were studied in rats with circumscribed unilateral lesions in the somatic sensorimotor cortex (SMC). Lesions were made in the caudal forelimb region (CFL), the rostral forelimb region (RFL), the anteromedial cortex (AMC) or the hindlimb area. Rats with damage in the CFL produced a deficit in placing the forelimb contralateral to the lesion during exploratory locomotion on a grid surface. Rats with AMC damage circled in the direction ipsilateral to the lesion. Lesions in the CFL or AMC produced an ipsilateral somatosensorimotor asymmetry on the bilateral-stimulation test (responding to adhesive patches placed on the contralateral forelimb was slower) that recovered in 7 days following AMC lesions or 28 days following CFL lesions. Finally, RFL lesions produced an ipsilateral asymmetry on the bilateral-stimulation task that was more severe and enduring (recovery in 60 days). After behavioral recovery, the effects of an additional lesion placed in the homotopic contralateral cortex were examined (two-stage bilateral lesion). Rats receiving two-stage bilateral lesions in the RFL or CFL responded slower to tactile stimulation of the forelimb contralateral to the second lesion. In the case of CFL-damaged rats, placing deficits also appeared contralateral to the most recent injury. In contrast, rats receiving two-stage bilateral AMC lesions did not exhibit behavioral asymmetries following the second lesion. These results provide evidence to suggest that subdivisions of the rat SMC can be distinguished with lesion/behavioral experiments. Moreover, a comparison of the effects of unilateral and two-stage bilateral lesions may help in the parcellation of the rat SMC into functionally distinct subareas and provide a basis for studying the processes of recovery and maintenance of function following brain damage.
Asunto(s)
Mapeo Encefálico , Dominancia Cerebral/fisiología , Miembro Anterior/inervación , Miembro Posterior/inervación , Regeneración Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Corteza Somatosensorial/fisiología , Animales , Locomoción/fisiología , Masculino , Actividad Motora/fisiología , Vías Nerviosas/fisiología , Orientación/fisiología , Ratas , Ratas Endogámicas , Tiempo de Reacción/fisiología , Conducta Estereotipada/fisiologíaRESUMEN
It has previously been shown that diazepam impairs behavioural recovery from partial unilateral ablation of the cerebral cortex in rats. The present study confirmed this in rats with large unilateral lesions of the frontal cortex and showed that diazepam (5 mg/kg i.p. daily for 14 days immediately after surgery) prevented recovery from sensory asymmetry even after 120 days. In saline-treated rats greater than 80% recovery had occurred by this time. A study of binding to benzodiazepine receptors, using an in vitro autoradiographic technique, was performed to determine whether the lack of recovery after administration of diazepam was associated with any long-term receptor changes on the damaged side of the brain. Binding of [3H]Ro15-1788 was increased by up to 40% in the caudate putamen on the decorticated side at 14-120 days. This was not significantly altered by treatment with diazepam. Binding of [3H]Ro15-1788 in the nucleus accumbens was not altered by lesion of the frontal cortex alone or after treatment with diazepam. It is concluded that the lack of recovery from sensory asymmetry, produced by diazepam after lesion of the frontal cortex cannot be correlated with any change in binding to benzodiazepine receptors within the corpus striatum.
Asunto(s)
Corteza Cerebral/fisiología , Cuerpo Estriado/metabolismo , Diazepam/farmacología , Receptores de GABA-A/metabolismo , Animales , Autorradiografía , Conducta Animal/efectos de los fármacos , Cuerpo Estriado/anatomía & histología , Flumazenil/metabolismo , Masculino , Núcleo Accumbens/anatomía & histología , Núcleo Accumbens/metabolismo , Ratas , Receptores de GABA-A/análisis , Factores de Tiempo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Sensorimotor function and the behavioural responses to a range of doses of subcutaneous apomorphine were assessed in mature (6-8 months) and old (23-26 months) Sprague-Dawley rats of comparable weight. In addition, the locomotor activity response of 12-month-old and 24-month-old rats to continuous infusions (14 days by osmotic minipump) of a selective dopamine D2 agonist. (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 10 micrograms/h) was investigated. Measures of spontaneous locomotor activity and motor coordination revealed impairments in the aged animals. Low doses of apomorphine (10-50 micrograms/kg), which preferentially activate dopamine autoreceptors, induced yawning, chewing mouth movements and penile grooming. The frequency of yawning and duration of penile grooming were significantly decreased in the old animals. In contrast, 200 micrograms/kg of apomorphine induced stereotyped sniffing and licking or gnawing, and these responses were significantly increased in the aged animals. There was a 25% decrease in striatal dopamine levels in the aged animals in this experiment. PHNO increased the amplitude of the circadian rhythms in locomotor activity exhibited by mature rats, and daytime tolerance to the stimulant effects of PHNO was reversed by stress in these animals. Both of these effects were attenuated in the aged rats. These findings suggest that (1) the dopamine receptors mediating yawning and stereotypy have different anatomical locations (2) ageing is associated with decreased responsiveness to stimulation of dopamine autoreceptors, consequent upon the loss of dopaminergic nerve terminals, and (3) while the functional response to selective stimulation of postsynaptic D2 receptors decreases with age, the postsynaptic response to a mixed D1/D2 agonist increases.
Asunto(s)
Envejecimiento/fisiología , Dopaminérgicos/farmacología , Actividad Motora/fisiología , Oxazinas/farmacología , Conducta Estereotipada/fisiología , Bostezo/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Apomorfina/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Endogámicas , Conducta Estereotipada/efectos de los fármacosRESUMEN
The role of the superior colliculus in multimodal sensory function is unsettled, in large part because a clear distinction between the somatosensory effects and the postural/motor effects of damage to the deep layers of the superior colliculus has not been obtained. Unilateral lesions of the entire superior colliculus impair orienting of the head and eyes to tactile, visual, and auditory stimuli presented on the side of the body contralateral to the lesion; however, even in the absence of sensory stimulation animals with such a lesion tend to circle ipsiversively and fail to make contralateral head movements. To determine whether or not unilateral damage to the superior colliculus produces a somatosensory asymmetry independently of head movement/circling biases, a neurological test was used in which lateral head or trunk movements were not required. Small pieces of adhesive-backed paper were attached to each forelimb and the latencies to contact and remove the stimuli were recorded. A battery of standard neurological tests was administered as well. The entire superior colliculus was removed unilaterally, and for comparison, the sensorimotor cortex or lateral hypothalamus were damaged in additional groups. Lesions of the superior colliculus produced the expected deficit in contralateral orienting and ipsilateral circling/postural biases, but failed to produce a somatosensory asymmetry in the head movement-independent sensorimotor test. In contrast, both sensorimotor cortex and lateral hypothalamus lesions produced a severe asymmetry in the head-movement-independent sensorimotor test. We conclude that the superior colliculus is involved in the control of lateral head movements and that its role in somatosensory function is fundamentally different from that of the sensorimotor cortex or lateral hypothalamus regions.
Asunto(s)
Área Hipotalámica Lateral/fisiología , Actividad Motora/fisiología , Corteza Somatosensorial/fisiología , Colículos Superiores/fisiología , Animales , Lateralidad Funcional/fisiología , Masculino , Orientación/fisiología , Postura , Ratas , Conducta Estereotipada/fisiologíaRESUMEN
Following unilateral damage to the anterior-medial region of the neocortex (AMC) in rats a sensory asymmetry appeared, but recovered within a week. In a separate group of rats with AMC lesions daily 3-week exposure to diazepam (Valium, 5 mg/kg) beginning 12 h after surgery caused recovery to be delayed indefinitely. The efficiency and speed (as opposed to symmetry) of behavior was not impaired. More than 9 weeks after discontinuation of diazepam (12 weeks postsurgery), recovery was still not apparent. Postmortem analysis ruled out lesion size as a contributing factor. In a second experiment undrugged animals with AMC lesions were allowed to recover for at least 3 weeks before being exposed to diazepam. These animals showed only a transient (2-day) reinstatement of asymmetry despite continuous drug treatment. We conclude that important mechanisms serving recovery of function may be vulnerable during a short period soon after brain damage.
Asunto(s)
Lesiones Encefálicas/fisiopatología , Diazepam/toxicidad , Regeneración Nerviosa/efectos de los fármacos , Animales , Lateralidad Funcional/fisiología , Masculino , Compresión Nerviosa , Neuronas Aferentes/efectos de los fármacos , Neuronas Aferentes/patología , Periodo Posoperatorio , Ratas , Ratas Endogámicas , Tiempo de Reacción/efectos de los fármacos , Corteza Somatosensorial/efectos de los fármacos , Corteza Somatosensorial/patología , Corteza Somatosensorial/fisiopatologíaRESUMEN
Three experiments were conducted with adult male Meriones unguiculatus in an attempt to demonstrate that ventral scent marking can act to transfer body heat to the object marked. Experiment 1 showed that surgical removal of the ventral gland pad reduced the amount of heat transferred by 50%, even though intact and glandless animals did not differ in the average frequency of scent marking. Experiment 2 demonstrated that the difference in heat transfer due to the presence or absence of the scent pad was not due to differential pressure applied to the substrate during marking. Experiment 3 showed that the pattern of ventral hair spread that occurs as an animal moves over an object is different between intact and glandless animals but that this difference does not account for the difference in heat transfer. It is suggested that heat transfer to the environment with ventral scent marking may increase thermoregulatory competence and also may function to volatilize sebum used in chemocommunication.
Asunto(s)
Comunicación Animal , Regulación de la Temperatura Corporal , Glándulas Exocrinas/fisiología , Gerbillinae/fisiología , Glándulas Odoríferas/fisiología , Animales , MasculinoRESUMEN
This experiment determined the effects of large unilateral lesions of the anteromedial cortex (AMC) on visually guided performance of rats in a cross maze. Deficits were found in the approach to only visual cues that were located in the arm contralateral to the lesion. The deficit appeared in three testing conditions: when the cue was continuously visible throughout the trial; when it was visible only at the choice point; and when it was seen only at the start of the trial but not at the choice point. The failure to approach a contralateral cue was not due to a simple ipsilateral turning bias; rats with lesions could approach cues in the anterior arm as efficiently as controls. The deficit was most apparent on the initial sessions and recovery occurred for all conditions. The findings indicate that the AMC participates in the visual guidance of approach behavior.