Muscarinic receptors 10 consciousness

The available data are consistent with the present thesis that cholinergic inputs to cerebral cortex mediate intradendritic events fundamental to conscious activity as a primary role, and that cholinergic modulation of electrophysiological activity may be secondary, even epiphenomenal. Transduction pathways exist whereby muscarinic receptors (and possibly nicotinic receptors acting presynaptically to inhibit acetylcholine release) may lead to actions on the cytoskeleton directly relevant to consciousness. The thesis presented here describes these pathways and also suggests a possible explanation for the diversity of neuromodulators and metabotropic receptors. Accordingly, qualitative aspects of our consciousness would be finely tuned by a number of neurochemicals, prominent among which is acetylcholine. 

Muscarinic receptor activation of cortical pyramidal cells occurs with a latency of around 250 msec (Taylor 8c Brown, 1999). There is also an approximate 500 msec time lag between the occurrence of a stimulus and consciousness of that stimulus (Libet et ah, 1991). Hence the typical delay associated with muscarinic action (and that of other metabotropic receptors) coincides with the time lag for stimuli reaching consciousness. Thus, cholinergic affer-ents to the cerebral cortex may contribute to 40 Hz activity, as well as to larger envelopes of activity (or inactivity) lasting 250-500 msec. 

Muscarinic receptor activation of an intradendritic site mediating conscious activity... 

Oyasu H, Yamamoto T, Sato N et al. (1994) Urinary bladder-selective action of the new antimuscarinic compound vamicamide. Arzneim Forsch/Drug Res 44 1242-1249 Peterson JS, Hanson RC, Noronha-Blob L (1989) In vivo cystometrogram studies in urethane-anesthetized and conscious guinea pigs. J Pharmacol Meth 21 231-241 Pietra C, Poggesi E, Angelico P et al. (1990) Effects of some antidepressants on the volume-induced reflex contractions of the rat urinary bladder lack of correlation with muscarinic receptors activity. Pharmacol Res 22 421-432 Postius S, Szelenyi I (1983) In vivo rat bladder a new model to screen spasmolytic compounds. J Pharmacol Meth 9 53-61... 

Ketamine appears to act similarly to phencyclidine (PCP also known as Angel Dust), which acts as an antagonist within the cationic channel of the NMDA receptor complex (36). By preventing the flow of cations through this channel, ketamine prevents neuronal activation, which normally is required for the conscious state. The analgesic activity of ketamine, however, is more likely the result of an interaction with an opioid receptor or the less-well-understood o-receptor. Other studies have suggested a possible involvement of serotonin receptors and muscarinic receptors (37). Ketamine, like PCP, has a significant potential for abuse. 

Of the different sensory modalities, olfaction does not appear to feature in reports of the effects of plant hallucinogens. Since olfaction is the one sense not relayed through the thalamus, this brain area is likely to be central to the changes in consciousness described. Many target receptors implicated, e.g. muscarinic, 5-HT2, D2, D3 and opiate, are present in this thalamic nuclei the human brain. 

Additionally, cardiac function can also be modulated by centrally-located H3-receptors. The intracerebroventricular administration of (R)a-methylhistamine in conscious animals is associated with a marked reduction of the heart rate, an effect which is antagonised by thioperamide (McLeod et al., 1991). The peripheral administration of ipratropium, a muscarinic antagonist which does not cross the blood-brain barrier, prevents such inhibition, demonstrating that the activation of centrally-located histamine H3-receptors leads to an increase in the vagal tone to the heart, rather than to a facilitatory effect on the sympathetic efferent fibers. 

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