Neuroscience
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The effect of systemically administered amphetamine, cocaine, phencyclidine and nomifensine on the extracellular concentrations of dopamine in freely moving rats was estimated by microdialysis in the nucleus accumbens and in the dorsal caudate. All the drugs tested stimulated dopamine output in both areas but more effectively in the accumbens as compared to the caudate. ⋯ The effect of cocaine, phencyclidine and nomifensine was prevented by systemic gamma-butyrolactone (700 mg/kg i.p.) and by omitting Ca2+ from the Ringer used for dialysis, the effect of amphetamine was insensitive to these manipulations. Thus, in contrast with amphetamine, cocaine, phencyclidine and nomifensine increase synaptic dopamine concentrations in vivo by a mechanism which depends on intact activity of dopaminergic neurons and by an exocytotic process.
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The detailed organization of the corticostriate projection has been investigated in the brain of the rat using the technique of retrograde transport of horseradish peroxidase following the placement of small, iontophoretic injections of horseradish peroxidase conjugated to lectin throughout all major regions of the striatum (caudate-putamen, nucleus accumbens and olfactory tubercle). The results demonstrate that all major regions of the cerebral cortex project to the striatum on both sides of the brain with an ipsilateral predominance. The cells of origin of both the ipsilateral and contralateral corticostriate projections lie mainly in lamina V (especially lamina Va) with very small numbers in lamina III of the neocortex and mesocortex, and in the deep laminae of the allocortex. ⋯ Within each of these major projection systems there is a further organization, with the constituent parts of each major cortical region projecting to smaller longitudinal components of the major projection fields. Each neocortical area projects to a longitudinal region of the dorsal striatum (caudate-putamen): the sensory and motor areas project topographically onto the dorsolateral striatum such that the rostral sensorimotor cortex (head areas) projects to central and ventral regions and the more caudal sensorimotor cortex (limb areas) projects to dorsal regions of the dorsolateral striatum; the visual area projects to the dorsomedial striatum; and the auditory area projects to the medial striatum. Each mesocortical area projects to a longitudinal area of the striatum: the most posteromedial mesocortex (the retrosplenial area) projects to the dorsomedial striatum; more anterior and lateral parts of the mesocortex project to more ventral parts of the striatum: and the most lateral mesocortex (the agranular insular and perirhinal areas) project to the ventrolateral striatum.(ABSTRACT TRUNCATED AT 400 WORDS)
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[125I]Iodosulpride, a highly selective and sensitive probe for dopamine D-2 receptors, was used to study the expression of these receptors in binding studies performed on membranes and serial autoradiographic sections, throughout pre- and postnatal developmental periods. D-2 receptors were first detected autoradiographically in sensory and sympathetic ganglia at the embryonic age of 12 days, i.e. much earlier than in previous studies. In membrane binding studies, D-2 receptors were found to be modulated by guanylnucleotides as early as at embryonic day 15, suggesting that they were already functionally coupled to a regulatory G protein. ⋯ In areas of dopaminergic perikarya, e.g. substantia nigra and ventral tegmental area, where they largely correspond to somatodendritic autoreceptors, D-2 receptors appeared at embryonic days 17 and 21 respectively, i.e. 3-8 days after tyrosine hydroxylase immunoreactivity, suggesting that dopamine synthesis and release is not feedback regulated by autoreceptors at initial developmental stages. In areas where D-2 receptors are present in the absence of any established dopaminergic innervation (e.g. discrete layers of the hippocampus, cerebellum, parietal cortex or in cranial nerve nuclei), they generally appeared at a late stage, i.e. during the second or even the third postnatal week. Finally, there was transient and roughly concomitant expression of both D-2 receptors and tyrosine hydroxylase immunoreactivity in some areas such as spinal ganglia or the lateral ventricle floor, consistent with a possible development function of dopamine mediated by D-2 receptors.
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Ablation of capsaicin-sensitive afferent neurons enhances experimentally induced ulceration in the rat gastric mucosa, which suggests that these neurons are involved in gastric mucosal protection. To provide direct evidence for such a function it was investigated whether stimulation of afferent nerve endings by the intragastric administration of capsaicin could counteract the ulcerogenic effect of 25% ethanol. Capsaicin (3.2-640 microM), administered together with ethanol, inhibited the development of haemorrhagic lesions in a concentration-dependent fashion but did not alter the ethanol-induced fall in the gastric potential difference. ⋯ The protective effect of intragastric capsaicin was not altered following acute subdiaphragmatic vagotomy, acute removal of the coeliac-superior mesenteric ganglion complex, acute bilateral ligation of the adrenal glands, or pretreatment of the rats with atropine or guanethidine. These findings indicate that stimulation of afferent neurons by intragastric capsaicin affords protection of the rat gastric mucosa against ethanol-induced damage. As the autonomic nervous system is not involved gastroprotection appears to represent a local effector function of sensory nerve endings in the stomach.
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Angiotensin II-(3-8)-hexapeptide, at the dose of 1 nmol given intracerebroventricularly, only slightly less than angiotensin II (the same dose and route) stimulated exploratory locomotor behaviour in an open field and electromagnetic motimeter. Both peptides considerably enhanced stereotyped behaviour produced by apomorphine and amphetamine. ⋯ The results indicate that the effectiveness of equimolar doses of angiotensin II-(3-8)-hexapeptide and angiotensin II in improving processes related to learning and memory in rats is almost identical and thus must be independent of specific angiotensin receptors in brain to which the hexapeptide binds with about 1000 times lower affinity than angiotensin II. The stimulation of stereotypy, a dopamine-controlled behaviour, by the peptides points to the possibility of dopaminergic mediation of their psychotropic effects.