Intracerebroventricular Injection Of 6-hydroxydopamine Research Articles

Effect of intracerebroventricular administration of chlorpromazine on the serum level of free fatty acids in rats.

The effect of intracerebroventricular administration of chlorpromazine (CPZ) on the serum level of free fatty acid (FFA) was studied in rats. Injection of CPZ into the lateral ventricle caused a transient decrease in serum FFA, showing the lowest level after 30 min. This decrease in serum FFA caused by CPZ was significantly inhibited by simultaneous injection of dopamine or apomorphine, although noradrenaline and serotonin had no effect. The dopaminergic blocking agent haloperidol caused a rapid decrease in serum FFA. After central chemical sympathectomy with the intracerebroventricular injection of 6-hydroxydopamine, the response to CPZ of serum FFA was completely abolished; but after peripheral sympathectomy by i.v. injection of 6-hydroxydopamine, a partial inhibition of the action of CPZ was shown. These results suggest a possible involvement of the central dopaminergic mechanism in the decrease in serum FFA after intracerebroventricular injection of CPZ.

Exaggerated sympathetic responses to bradykinin in spontaneously hypertensive rats.

Possible defects in blood pressure (BP) regulation were studied by recording responses to centrally-administered bradykinin. Pressor effects accompanied by increased sympathetic nerve activity were elicited by intracerebroventricular injections in intact rats, but significant differences between Kyoto-Wistar normotensive (KNR) and spontaneously hypertensive rats (SHR) were not detected. By contrast, intracarotid injections into cross-perfused head preparations consistently produced more prominent systemic effects in SHR than in KNR, and these differences became even more pronounced following carotid denervation. After destruction of central noradrenergic neurons in KNR by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA), responses to bradykinin became the same as those in SHR. These results are in accord with the interpretation that alpha-adrenergic mechanisms for blood pressure regulation in supramedullary brain areas no longer function normally in SHR and that a similar dysfunction can be induced in KNR by pretreatment with 6-OHDA.

The effect of cyclo (Leu-Gly) on chemical denervation supersensitivity of dopamine receptors induced by intracerebroventricular injection of 6-hydroxydopamine in mice

Chemical denervation supersensitivity of postsynaptic dopamine receptors was induced in mice by intracerebroventricular injection of 6-hydroxydopamine. Fourteen days after the 6-hydroxydopamine injection, mice exhibited greater spontaneous locomotor activity and hypothermic response when challenged intraperitoneally with apomorphine. Whole brain levels of dopamine were reduced by 80%. Daily subcutaneous administration of cyclo (Leu-Gly) (50 μg/mouse/day) for 14 days inhibited the development of dopamine receptor supersensitivity induced by 6-hydroxydopamine as evidenced by the blockade of an apomorphine induced locomotor and hypothermic effect. Cyclo (Leu-Gly) did not alter the depletion of brain dopamine induced by 6-hydroxydopamine. These data suggest that cyclo (Leu-Gly) can block the development of dopamine receptor supersensitivity induced by 6-hydroxydopamine without protecting the neurons from dopamine depletion.

Presynaptic inhibition leading to disinhibition of acetylcholine release from interneurons of the caudate nucleus: Effects of dopamine, β-endorphin and d-Ala 2-Pro 5-enkephalinamide

The release of acetylcholine from slices of the rat striatum has been studied in two groups of animals: untreated rats and rats pretreated by intracerebroventricular injections of 6-hydroxydopamine in doses sufficient partially or completely to destroy the nigrostriatal dopaminergic tract. The amount of acetylcholine released was much greater, both under resting conditions and in the presence of ouabain. from striatal slices from the latter group. Dopamine, β-endorphin, d-Ala 2-Pro 5-enkephalinamide and morphine enhanced the ouabain-induced release of acetylcholine from normal striatal slices, but inhibited the release of acetylcholine from striatal slices of 6-hydroxydopamine pretreated rats Naloxone prevented the effects of the opioid peptides. Thus there appear to be receptors, both on the cholinergie interneurons of the striatum and on the terminals of dopaminergic fibres, which are sensitive to dopamine, β-endorphin, enkephalin and morphine. Dopamine, released from nigrostriatal neurons, inhibits acetylcholine release from striatal interneurons. It is suggested that β-endorphin, or some other enkephalin-like peptide present in the striatum, might moderate the dopaminergic inhibition of acetylcholine release by presynaptically inhibiting the release of dopamine. A disinhibition phenomenon of this type might play an important role in the modulation of neurochemical transmission.