RESUMEN
Male rats received a dopaminergic implant aimed either at the nucleus accumbens or the ventral tegmental area (VTA) following 6-hydroxydopamine lesion of their mesocorticolimbic dopaminergic system. Exposure to electrical footshock stress 6 months later markedly activated the mesocorticolimbic neurons in control animals as shown by the increase of dihydroxyphenylacetic acid (DOPAC) levels both in the nucleus accumbens and the VTA. However, no stress-induced activation was seen for the grafted neurons, irrespective of the area of implantation. These results indicate the lack of reinnervation and modulation of the grafted dopaminergic neurons by one of the important afferent systems regulating the activity of endogenous mesencephalic dopaminergic neurons.
Asunto(s)
Dopamina/fisiología , Electrochoque , Actividad Motora/fisiología , Núcleo Accumbens/trasplante , Núcleos Septales/trasplante , Tegmento Mesencefálico/trasplante , Ácido 3,4-Dihidroxifenilacético/metabolismo , Vías Aferentes/fisiología , Animales , Dopamina/metabolismo , Supervivencia de Injerto , Hidroxidopaminas , Masculino , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Oxidopamina , Ratas , Ratas Endogámicas , Tegmento Mesencefálico/efectos de los fármacos , Tegmento Mesencefálico/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Dissection techniques and optimal donor stages have been established for constructing an isolated intraocular model of the ventral tegmental area (VTA)-accumbens system using intraocular sequential grafting. Single grafts including accumbens and VTA respectively survived and developed many organotypic features when taken from 15-17 day fetuses. Falck-Hillarp fluorescence histochemistry showed dopamine neurons and terminals in single VTA grafts, no or almost no catecholamine fibers in single accumbens grafts, and a well-developed VTA-accumbens dopamine pathway in combined grafts where cell bodies in the VTA part provided the accumbens part with a rich terminal network. A similar distribution was found using immunohistochemistry with antibodies directed against tyrosine hydroxylase. CCK-like immunoreactivity had a distribution that mimicked that of the catecholamine-containing system. Enkephalin-like immunoreactivity was found both in single VTA and in single accumbens pieces as well as in both parts of the double grafts. Cells with long-duration action potentials typical of dopamine neurons discharged at approximately 8 Hz in single VTA grafts and below 1 Hz in the VTA part of VTA-accumbens double grafts. Cells in the accumbens portion of double grafts had shorter action potential durations and fired at 10-20 Hz. Haloperidol increased discharge frequency in VTA neurons with long action potential durations while apomorphine reduced discharge markedly. Antidromic activation of putative dopamine neurons in the VTA part was obtained by electrical stimulation of the accumbens part. The indirect dopamine agonist + 3-methyl-phencyclidine slowed firing rates of neurons in the accumbens part of double grafts. Taken together, the histochemical and the electrophysiological data show that the intraocular VTA-accumbens system retains several of its normal structural and functional characteristics. It is proposed that the isolated VTA-accumbens projection can be used as a model to study the cellular mechanism of action of stimulant and opiate drugs of abuse.