RESUMEN
The bacterial endotoxin lipopolysaccharide (LPS) exerts strong effects on the immune-neuroendocrine network. On behaviour, LPS induces the symptoms of sickness behaviour. Otherwise, LPS challenge shares with psychological stress some common physiological adaptations. The proposal of this study was to analyse the effects of the LPS injection on the behavioural response in the shock-probe defensive burying test of two wild house mouse lines genetically selected for short (SAL) and long (LAL) latency to attack a conspecific. It is known that with previous exposure to stress, each of these lines exhibits behaviour in the burying test that is closely related to their different neuroendocrine patterns of response, with higher expression of burying in the SAL and immobility in the LAL mice. LPS (0.5 ml, 375 microg/Kg) or sterile saline (0.9%) was i.p. injected 3.5h before the beginning of the test. Non-injected mice were used as a general control of stress of handling and drug effect. The following behaviours were analyzed: defensive burying, immobility, rearing, grooming, exploration and jumping. The procedure of injection was found to be a stimulus that induced behavioural alterations in the SAL and LAL mice. Some behavioural changes induced by saline injection resembled that induced by LPS injection; in both lines an increase in immobility as well as a decrease in burying behaviour was observed. It is noteworthy that the LAL mice increased more their immobility than the SAL mice after saline or LPS injection, and the decrease in burying in the saline and LPS-injected mice was lower in the SAL than in the LAL mice. These results and others discussed in the text suggest that the active coping strategy of SAL mice and the passive coping strategy of the LAL mice, the hallmark of each line in the shock-probe burying test is present after psychological as well as LPS challenge exposure.
Asunto(s)
Agresión/fisiología , Reacción de Prevención/fisiología , Conducta Animal/fisiología , Lipopolisacáridos/inmunología , Estrés Psicológico/inmunología , Adaptación Fisiológica/genética , Agresión/psicología , Análisis de Varianza , Animales , Electrochoque , Pérdida de Tono Postural/fisiología , Lipopolisacáridos/farmacología , Masculino , Ratones , Neuroinmunomodulación/inmunología , Tiempo de Reacción/genética , Especificidad de la Especie , Estrés Psicológico/genética , Estrés Psicológico/psicologíaRESUMEN
It has been reported that the ACTH-(4-9) analog H-Met(O(2))-Glu-His-Phe-D-Lys-Phe-OH (ORG 2766) administered in adulthood has trophic effects on neuronal tissue and when given postnatally, it can induce long-lasting changes in brain development. In the present study, we investigated whether early postnatal treatment with ORG 2766 affects adult neuronal vulnerability, i.e. the sensitivity of cholinergic neurons against excitotoxic damage. Wistar rat pups received injections of ORG 2766 or saline on postnatal days 1, 3 and 5 and were then left undisturbed until adulthood. At the age of 6 months, the animals were subjected to unilateral lesion of magnocellular basal nucleus by infusion of high dose of N-methyl-D-aspartate (NMDA). The effects of the excitotoxic insult were studied 28 hours and 12 days after the lesion by measuring both the acute cholinergic and glial responses, and the final outcome of the degeneration process. Twenty eight hours after NMDA infusion, postnatally ACTH-(4-9)-treated animals showed stronger suppression of choline-acetyltransferase immunoreactivity and increased reaction of glial fibrillary acidic protein -immunopositive astrocytes in the lesioned nucleus compared to control animals. However, 12 days post-surgery, the NMDA-induced loss of cholinergic neurons, as well as the decrease of their acetylcholinesterase -positive fibre projections in the cortex, were less in ACTH-(4-9) animals. Our data indicate that the early developmental effects of ACTH-(4-9) influence intrinsic neuroprotective mechanisms and reactivity of neuronal and glial cells, thereby resulting in a facilitated rescuing mechanism following excitotoxic injury.
Asunto(s)
Hormona Adrenocorticotrópica/análogos & derivados , Hormona Adrenocorticotrópica/farmacología , Animales Recién Nacidos/fisiología , Núcleo Basal de Meynert/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , N-Metilaspartato/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Acetilcolinesterasa/metabolismo , Animales , Astrocitos/efectos de los fármacos , Núcleo Basal de Meynert/enzimología , Núcleo Basal de Meynert/patología , Recuento de Células , Colina O-Acetiltransferasa/metabolismo , Agonistas de Aminoácidos Excitadores/toxicidad , Proteína Ácida Fibrilar de la Glía/metabolismo , Inmunohistoquímica , N-Metilaspartato/toxicidad , Ratas , Ratas WistarRESUMEN
The present study demonstrates the effects of adrenalectomy and subcutaneously administered corticosterone on N-methyl-D-aspartate-induced neurodegeneration in the cholinergic magnocellular basal nucleus of the rat. NMDA was unilaterally injected into the nucleus basalis at different plasma corticosterone concentrations in adrenalectomized rats, in adrenalectomized animals with subcutaneously implanted cholesterol-corticosterone pellets containing 25% or 100% corticosterone, and in sham-adrenalectomized controls. The neurotoxic impact of the NMDA injection in the various experimental groups was assessed by the loss of cholinergic fibers stained with acetylcholinesterase histochemistry in the parietal neocortex. Reactive cortical astrocytes as a result of the treatments were detected by glial fibrillary acidic protein immunohistochemistry. Measurements of the densities of astrocytes and cholinergic fibers at the injected side of the brain were carried out by image analysis. Adrenalectomy significantly potentiated the NMDA-induced neurodegeneration by 50%, while chronic administration of corticosterone significantly attenuated the NMDA-neurotoxicity in a dose-dependent manner. Compared to the ADX group, 25% corticosterone application reduced the NMDA damage by 37%, whereas the 100% corticosterone pellet diminished NMDA neurotoxicity by 75%. Both ADX and ADX + corticosterone implantation enhanced the NMDA-induced GFAP immunoreactivity. The increase of GFAP immunoreactivity was most pronounced in the adrenalectomized rats supplied with the 100% corticosterone pellets. The results demonstrate that corticosterone exerts a potent neuroprotective effect on NMDA-induced neurotoxicity in the magnocellular nucleus basalis. The activated astroglia suggest that astrocytes may contribute to the beneficial effect of corticosterone in the neuroprotective mechanisms against excitotoxic neuronal injury.
Asunto(s)
Adrenalectomía , Fibras Colinérgicas/efectos de los fármacos , Corticosterona/sangre , N-Metilaspartato/toxicidad , Sustancia Innominada/citología , Sustancia Innominada/efectos de los fármacos , Acetilcolinesterasa/análisis , Animales , Astrocitos/citología , Astrocitos/efectos de los fármacos , Astrocitos/enzimología , Muerte Celular/efectos de los fármacos , Corticosterona/farmacología , Proteína Ácida Fibrilar de la Glía/análisis , Inmunohistoquímica , Masculino , Degeneración Nerviosa , Ratas , Ratas WistarRESUMEN
The (+) enantiomer of the very potent and selective dopamine D-2 agonist, 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437), displays partial agonistic activity at dopamine D-2 receptors. In this study (+)N-0437 was investigated for its antagonistic activity at postsynaptic DA receptors in four behavioural tests which are commonly used to evaluate potential neuroleptic activity, i.e. d-amphetamine-induced stereotypy, passive avoidance responding, intracranial self-stimulation behaviour, and catalepsy. (+)N-0437 (25-50 mumol/kg) was active in the first three models, but did not cause catalepsy. Haloperidol, which was used as a reference compound for classical DA antagonists, showed clear activity in all four models at low doses (0.5-1.0 mumol/kg). (-)N-0437, a full D-2 agonist, displayed no activity in these behavioural models. These results suggest that (+)N-0437 could be used to examine the hypothesis that the use of partial agonists could provide a new treatment for schizophrenia.