Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens

Pijnenburg, Annick; Rossum, J. M. van

doi:10.1111/j.2042-7158.1973.tb09995.x

Cited by 458 publications

(72 citation statements)

References 7 publications

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“…Because spontaneous locomotion is believed to be primarily mediated by the mesolimbic DA system (Pijenburg and Van Rossum 1973), these results suggest that mesolimbic DA receptors were blocked during con tinuous exposure to haloperidol but not to clozapine.…”

Section: Discussionmentioning

confidence: 70%

Subchronic Treatment with Haloperidol and Clozapine in Rats with Neonatal Excitotoxic Hippocampal Damage

Lipska

Weinberger

1994

Neuropsychopharmacol

125

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We have previously demonstrated that rats with neonatal excitotoxic hippocampal damage manifest abnormal dopamine (DA)-related behaviors after puberty, a phenomenon that has implications for an animal model of schizophrenia. In this study we investigated the effects of subchronic treatment with haloperidol and clozapine in these animals. The ventral hippocampus (VH) of rat pups was lesioned with ibotenic acid on postnatal day 7 (PD7). Starting at PD56, rats were treated for 21 days with either vehicle (VEH), haloperidol (HAL) (0.1 mglkg, IP), or clozapine (CLOZ) (4 mglkg, IP). Spontaneous locomotor activity was measured 0.5 hour after the last injection. Apomorphine (APO)-induced stereotypy and locomotion were evaluated five days later. The VH lesioned rats treated with VEH expressed enhanced novelty-and apomorphine-induced hyperlocomotion, as well as potentiated apomorphine-induced stereotypic behaviors as compared to sham-Iesioned counterparts. Spontaneous locomotor activity was suppressed by haloperidol but not by clozapine in the sham-operated group, whereas both drugs were effective in suppressing hyperlocomotion in the VH lesioned rats. Withdrawal supersensitivity to apomorphine was seen in the haloperidol but not in the clozapine-treated lesioned rats, and none of the drugs produced significant supersensitivity in the sham-operated animals. These results indicate that the two neuroleptics exerted differential behavioral effects in neurologically intact and hippocampally lesioned animals, and that these effects were also drug-specific.

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Section: Discussionmentioning

confidence: 70%

Subchronic Treatment with Haloperidol and Clozapine in Rats with Neonatal Excitotoxic Hippocampal Damage

Lipska

Weinberger

1994

Neuropsychopharmacol

125

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“…Still, there is evidence that low doses of ethanol increase the firing rate of dopam inergic cells in the ventral tegmental area (Gessa et al 1985) and enhance the release of dopam ine in the nucleus accumbens (Di Chiara and Im perato 1985). Since such enhanced dopaminergic activity produces an increase in loco m otor activity (Pijnenburg and van Rossum 1973;Pijnenburg et al 1975), it is reasonable to suggest that this mechanism gave rise to the excitatory effects seen in HR. Indeed, the dopam ine activity in the nucleus accumbens of habituated rats is low, but increases in non-habituated rats (Cools et al 1993a, b;Rots et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Gingras

Cools

1996

Psychopharmacology

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The aim of the study was to investigate the biphasic locom otor response to ethanol in rats. Based on the recent finding that high responders to novelty (HR) and low responders to novelty (LR), selected from an outbred Nijmegen W istar rat population, show differences in ethanol intake and preference, it was ini tially investigated to what extent H R and L R differ in their locom otor response to ethanol, A dose-response curve (0.2-2.0 g/kg, IP) was established using stan dardized activity boxes. H R showed a significant increase at 0.5 g/kg, followed by a significant decrease at doses 1.0-2.0 g/kg; LR showed only a decrease at doses 1.0-2.0 g/kg. Secondly, it was investigated to what extent stress altered the ethanol-induced increase and decrease, respectively. For that purpose, the ethanol-induced locom otor effects (0.5 and 1.0 g/kg) were analyzed in habituated and noil-habituated (stressed) H R and LR; habituation consisted of a 15-min adaptation period to the activity cages. Stress significantly enhanced the excitatory effects in H R , but had no effect on the sedative effects in H R and LR. Finally, the locom otor effects of sub-chronic treatm ent (7 days) with an excitatory (0.5 g/kg) or sedative (LO g/kg) dose were analyzed in H R and LR. The excitatory effect of 0.5 g /k g disappeared throughout the treatm ent in H R , whereas the sedative effects of 1.0 g/kg remained the same in H R and LR. It is con cluded that the mechanism underlying the ethanolinduced m otor excitation differs completely from that underlying the ethanol-induced sedation. Given the known differences in the m ake-up of the brain and endocrine system between H R and LR, these animals are suggested to be good models for studying the m ech anisms underlying the biphasic locom otor response to ethanol in rats.

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“…Sin embargo, el animal crónico tiende a un estado depresivo cuyo sustrato neurobioquímico sería exacta-mente la disminución de la actividad dopami-nérgica. Se conoce de la capacidad excitatoria directa por la dopamina (43)(44)(45)(46).…”

Section: Discussionunclassified

Importancia dopaminérgica en farmacodinamia de cocaína evaluada por alteraciones de GABA y glutamato en el núcleo accumbens de ratas

Gélvez¹,

Pastrana²,

Ulloque³

1996

biomedica

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ResumenEste trabajo se propuso demostrar la importancia del sistema dopaminérgico en la farmacodinamia de cocaína en el SNC de ratas. Este postulado se verificó evaluando las alteraciones de GABA y glutamato en el núcleo accumbens.Este enfoque se sustenta en la gran cantidad de evidencias que muestran, consistentemente alteraciones en la actividad dopaminérgica por cocaína. Además, el GABA y el glutamato tienen gran importancia en los efectos agudos y crónicos por cocaína. Es bien conocida la interrelación de GABA y glutamato con la actividad dopaminérgica en el núcleo accumbens.Se diseñó un estudio por 16 días de administración de cocaína a ratas a la dosis inicial de 30 mglkgldía (IP) con incremento de 5 mglkg cada 4 días, a las cuales se les había lesionado la actividad dopaminérgica en el núcleo accumbens con la neurotoxina 6-hidroxidopamina en ácido ascórbico. Además, se conformó un grupo basal que recibió estereotáxicamante, en el núcleo accumbens, ácido ascórbico en solución salina 0,9% y se trató con un volumen correspondiente de solución salina (IP) y, un grupo control, al cual estereotáxicamente, en el núcleo mencionado, se le administró 6-OHDA (en ácido ascórbico), recibiendo posteriormente como tratamiento solución salina (IP). La determinación de los niveles de GABA y glutamato se realizó por métodos enzimáticos.Se observó que la administración crónica de cocaína produce una disminución significativa en el nivel de GABA en el núcleo accumbens del grupo problema, con relación a los grupos basal y control. En tanto, el nivel de glutamato en el grupo problema mostró un incremento significativo con relación al grupo basal, pero, no con relación al grupo control.En conclusión, los resultados de este trabajo sostienen la hipótesis del papel importante que tiene la dopamina en la farmacoterapia de cocaína a través de las alteraciones en los niveles de GABA y glutamato o alteraciones en forma directa. Además, la cocaína podría alterar por sí misma la actividad gabaérgica y glutaérgica. SummaryThe aim of the present study was to investigate the role of dopamine in cocaine pharmacodynamics in rats. To test this hypothesis, we measured GABA and glutamate level changes in the accumbens nucleus. This approach is supported by the preponder-

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Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens

Cited by 458 publications

References 7 publications

Subchronic Treatment with Haloperidol and Clozapine in Rats with Neonatal Excitotoxic Hippocampal Damage

Subchronic Treatment with Haloperidol and Clozapine in Rats with Neonatal Excitotoxic Hippocampal Damage

Analysis of the biphasic locomotor response to ethanol in high and low responders to novelty: a study in nijmegen wistar rats

Importancia dopaminérgica en farmacodinamia de cocaína evaluada por alteraciones de GABA y glutamato en el núcleo accumbens de ratas

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