Abstract
The behavioural and electrocortical (ECoG) effects of clonidine were studied after microinjection into the third cerebral ventricle, or microinfusion into some specific areas of the rat brain rich in noradrenaline-containing cell bodies (locus coeruleus) or into areas receiving noradrenergic terminals (dorsal hippocampus, amygdaloid complex, thalamus, frontal and sensimotor cortex). The ECoG effects were continuously analysed and quantified by means of a Berg-Fourier analyser as total power and as power in preselected bands of frequency. Clonidine (9.4 to 75 nmol) given into the third cerebral ventricle produced behavioural sedation and sleep and a dose-dependent increase in ECoG total voltage power as well as in the lower frequency bands. Much lower doses were required to produce similar behavioural and ECoG spectrum power effects after either unilateral or bilateral microinfusion of clonidine into the locus coeruleus. Doses of clonidine equimolar to those given into the third cerebral ventricle, were almost ineffective in inducing behavioural and ECoG sleep after their microinfusion into the dorsal hippocampus. In addition, a dose (0.56 nmol) of clonidine which, given into the locus coeruleus, produced marked behavioural sleep and ECoG synchronization, lacked effects when given into the ventral or anterior thalamus, into the amygdaloid complex or onto the frontal and sensimotor cortex. The behavioural and ECoG spectrum power effects of clonidine given into the third cerebral ventricle or into the locus coeruleus were prevented by antagonists of alpha 2-adrenoceptors but not by alpha 1-adrenoceptor antagonists. Intraventricular microinjection, or microinfusion into the locus coeruleus, of yohimbine, a selective alpha 2-adrenoceptor antagonist, produced behavioural arousal, increase in locomotor and exploratory activity, tachypnoea and ECoG desynchronization with a significant reduction in total voltage power. Similar stimulatory effects were also observed after microinjection of phentolamine into the same sites. No significant effects on behaviour and ECoG activity were evoked after intraventricular injection or microinfusion into the locus coeruleus of prazosin or methoxamine.
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Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aghajanian G. K., VanderMaelen C. P. alpha 2-adrenoceptor-mediated hyperpolarization of locus coeruleus neurons: intracellular studies in vivo. Science. 1982 Mar 12;215(4538):1394–1396. doi: 10.1126/science.6278591. [DOI] [PubMed] [Google Scholar]
- Amaral D. G., Sinnamon H. M. The locus coeruleus: neurobiology of a central noradrenergic nucleus. Prog Neurobiol. 1977;9(3):147–196. doi: 10.1016/0301-0082(77)90016-8. [DOI] [PubMed] [Google Scholar]
- Aston-Jones G., Bloom F. E. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J Neurosci. 1981 Aug;1(8):876–886. doi: 10.1523/JNEUROSCI.01-08-00876.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aston-Jones G., Bloom F. E. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli. J Neurosci. 1981 Aug;1(8):887–900. doi: 10.1523/JNEUROSCI.01-08-00887.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradshaw C. M., Pun R. Y., Slater N. T., Szabadi E. Comparison of the effects of methoxamine with those of noradrenaline and phenylephrine on single cerebral cortical neurones. Br J Pharmacol. 1981 May;73(1):47–54. doi: 10.1111/j.1476-5381.1981.tb16770.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bricolo A., Turazzi S., Faccioli F., Odorizzi F., Sciaretta G., Erculiani P. Clinical application of compressed spectral array in long-term EEG monitoring of comatose patients. Electroencephalogr Clin Neurophysiol. 1978 Aug;45(2):211–225. doi: 10.1016/0013-4694(78)90005-6. [DOI] [PubMed] [Google Scholar]
- Cavero I., Roach A. G. The effects of prazosin on the clonidine induced hypotension and bradycardia in rats and sedation in chicks [proceedings]. Br J Pharmacol. 1978 Mar;62(3):468P–469P. [PMC free article] [PubMed] [Google Scholar]
- Cespuglio R., Gomez M. E., Faradji H., Jouvet M. Alterations in the sleep-waking cycle induced by cooling of the locus coeruleus area. Electroencephalogr Clin Neurophysiol. 1982 Nov;54(5):570–578. doi: 10.1016/0013-4694(82)90042-6. [DOI] [PubMed] [Google Scholar]
- Clark T. K. The locus coeruleus in behavior regulation: evidence for behavior-specific versus general involvement. Behav Neural Biol. 1979 Mar;25(3):271–300. doi: 10.1016/s0163-1047(79)90393-5. [DOI] [PubMed] [Google Scholar]
- De Jong W., Nijkamp F. P. Centrally induced hypotension and bradycardia after administration of alpha-methylnoradrenaline into the area of the nucleus tractus solitarii of the rat. Br J Pharmacol. 1976 Dec;58(4):593–598. doi: 10.1111/j.1476-5381.1976.tb08628.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Drew G. M., Gower A. J., Marriott A. S. Alpha 2-adrenoceptors mediate clonidine-induced sedation in the rat. Br J Pharmacol. 1979 Sep;67(1):133–141. [PMC free article] [PubMed] [Google Scholar]
- Hobson J. A., McCarley R. W., Wyzinski P. W. Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science. 1975 Jul 4;189(4196):55–58. doi: 10.1126/science.1094539. [DOI] [PubMed] [Google Scholar]
- Koella W. P. The organization and regulation of sleep. A review of the experimental evidence and a novel integrated model of the organizing and regulating apparatus. Experientia. 1984 Apr 15;40(4):309–338. doi: 10.1007/BF01952538. [DOI] [PubMed] [Google Scholar]
- Langer S. Z. Presynaptic regulation of catecholamine release. Biochem Pharmacol. 1974 Jul 1;23(13):1793–1800. doi: 10.1016/0006-2952(74)90187-7. [DOI] [PubMed] [Google Scholar]
- Marley E. Central effects of clonidine 2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride in fowls. Br J Pharmacol. 1975 Dec;55(4):459–473. doi: 10.1111/j.1476-5381.1975.tb07421.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marley E., Nisticò G. Pharmacological basis of arousal and sleep in chickens (Gallus domesticus). Pharmacol Res Commun. 1983 Feb;15(2):111–118. doi: 10.1016/s0031-6989(83)80053-8. [DOI] [PubMed] [Google Scholar]
- Monti J. M. Catecholamines and the sleep-wake cycle. I. EEG and behavioral arousal. Life Sci. 1982 Apr 5;30(14):1145–1157. doi: 10.1016/0024-3205(82)90656-7. [DOI] [PubMed] [Google Scholar]
- Morrison J. H., Grzanna R., Molliver M. E., Coyle J. T. The distribution and orientation of noradrenergic fibers in neocortex of the rat: an immunofluorescence study. J Comp Neurol. 1978 Sep 1;181(1):17–39. doi: 10.1002/cne.901810103. [DOI] [PubMed] [Google Scholar]
- Petitjean F., Sakai K., Blondaux C., Jouvet M. Hypersomnie par lésion isthmique chex le chat. II. Etude neurophysiologique et pharmacologique. Brain Res. 1975 May 9;88(3):439–453. doi: 10.1016/0006-8993(75)90656-3. [DOI] [PubMed] [Google Scholar]
- Philippu A., Schartner P. Inhibition by locally applied alpha-adrenoreceptor blocking drugs of the depressor response to stimulation of the anterior hypothalamus. Naunyn Schmiedebergs Arch Pharmacol. 1976 Oct;295(1):1–7. doi: 10.1007/BF00509764. [DOI] [PubMed] [Google Scholar]
- Ramm P. The locus coeruleus, catecholamines, and REM sleep: a critical review. Behav Neural Biol. 1979 Apr;25(4):415–448. doi: 10.1016/s0163-1047(79)90212-7. [DOI] [PubMed] [Google Scholar]
- Redmond D. E., Jr, Huang Y. H., Snyder D. R., Maas J. W. Behavioral effects of stimulation of the nucleus locus coeruleus in the stump-tailed monkey Macaca arctoides. Brain Res. 1976 Nov 12;116(3):502–510. doi: 10.1016/0006-8993(76)90498-4. [DOI] [PubMed] [Google Scholar]
- Rotiroti D., Silvestri R., de Sarro G. B., Bagetta G., Nisticò G. Evidence that behavioural and electrocortical sleep induced by guanfacine is due to stimulation of alpha 2-adrenoceptors. J Psychiatr Res. 1982;17(3):231–239. doi: 10.1016/0022-3956(82)90001-2. [DOI] [PubMed] [Google Scholar]
- Schmitt H., Fenard S. Evidence for an alpha-sympathomimetic component in the effects of catapresan on vasomotor centres: antagonism by piperoxane. Eur J Pharmacol. 1971;14(1):98–100. doi: 10.1016/0014-2999(71)90130-0. [DOI] [PubMed] [Google Scholar]
- Sinha J. N., Gurtu S., Sharma D. K., Bhargava K. P. An analysis of the alpha-adrenoceptor modulation of vasomotor tone at the level of lateral medullary pressor area (LMPA). Naunyn Schmiedebergs Arch Pharmacol. 1985 Sep;330(3):163–168. doi: 10.1007/BF00572428. [DOI] [PubMed] [Google Scholar]
- Starke K. Alpha-adrenoceptor subclassification. Rev Physiol Biochem Pharmacol. 1981;88:199–236. [PubMed] [Google Scholar]
- Steriade M., Hobson J. Neuronal activity during the sleep-waking cycle. Prog Neurobiol. 1976;6(3-4):155–376. [PubMed] [Google Scholar]
- Svensson T. H., Bunney B. S., Aghajanian G. K. Inhibition of both noradrenergic and serotonergic neurons in brain by the alpha-adrenergic agonist clonidine. Brain Res. 1975 Jul 11;92(2):291–306. doi: 10.1016/0006-8993(75)90276-0. [DOI] [PubMed] [Google Scholar]
- Tanaka C., Inagaki C., Fujiwara H. Labeled noradrenaline release from rat cerebral cortex following electrical stimulation of locus coeruleus. Brain Res. 1976 Apr 23;106(2):384–389. doi: 10.1016/0006-8993(76)91034-9. [DOI] [PubMed] [Google Scholar]
- Timmermans P. B., Schoop A. M., Kwa H. Y., Van Zwieten P. A. Characterization of alpha-adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine and corynanthine. Eur J Pharmacol. 1981 Mar 5;70(1):7–15. doi: 10.1016/0014-2999(81)90426-x. [DOI] [PubMed] [Google Scholar]
- Ungerstedt U. Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand Suppl. 1971;367:69–93. doi: 10.1111/j.1365-201x.1971.tb11000.x. [DOI] [PubMed] [Google Scholar]
- Young W. S., 3rd, Kuhar M. J. Noradrenergic alpha 1 and alpha 2 receptors: light microscopic autoradiographic localization. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1696–1700. doi: 10.1073/pnas.77.3.1696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zebrowska-Lupina I., Kleinrok Z. Behavioural effects of yohimbine administered intraventricularly in the rat. Psychopharmacologia. 1973;33(3):267–275. doi: 10.1007/BF00423061. [DOI] [PubMed] [Google Scholar]