The in vivo neurochemistry of the brain during general anesthesia

Abstract

J. Neurochem. (2011) 119, 419–446. Abstract Anesthesia describes a complex state composed of immobility, amnesia, hypnosis (sleep or loss of consciousness), analgesia, and muscle relaxation. Bottom‐up approaches explain anesthesia by an interaction of the anesthetic with receptor proteins in the brain, whereas top‐down approaches consider predominantly cortical and thalamic network activity and connectivity. Both approaches have a number of explanatory gaps and as yet no unifying view has emerged. In addition to a direct interaction with primary target receptor proteins, general anesthetics have massive effects on neurotransmitter activity in the brain. They can change basal transmitter levels by interacting with neuronal activity, transmitter synthesis, release, reuptake and metabolism. By that way, they can affect a great number of neurotransmitter systems and receptors. Here, we review how different general anesthetics affect extracellular activity of neurotransmitters in the brain during induction, maintenance, and emergence from anesthesia and which functional consequences this may have. Commonalities and differences between different groups of anesthetics in their action on neurotransmitter activity are discussed. We also review how general anesthetics affect the response dynamics of the neurotransmitter systems after sensory stimulation. More than 30 years of research have now yielded a complex picture of the effects of general anesthetics on brain neurotransmitter basal activity and response dynamics. It is suggested that analyzing the effects on neurotransmitter activity is the logical next step after protein interactions in a bottom‐up analysis of anesthetic action in the brain on the way to a unifying view of anesthesia.

NMDA Receptor Antagonist Ketamine Impairs Feature Integration in Visual Perception

“…These conflicting results could be due to a combination of dose, task differences between the experiments and pharmacological profile. Although NMDA receptors are the primary target for ketamine, ketamine has a complex pharmacological profile and it exerts some additional effects on various other signaling pathways, such as dopamine, opioid, mono-aminergic, cholinergic, nicotinic, muscarinic, serotonergic, GABAergic and AMPA receptors [50–52]. Those interactions may also contribute to the observed effects, and the differential effects observed for ketamine and dextrometorphan (that has multiple mechanisms of action as well, such as sigma-1 receptor antagonism [53]).…”

Psychostimulants

“…Mental states control subjective perception, memory retrieval, and autonomic and behavioral responses (White, 1996). The mental states of the brain are determined by the different functional states of the modulatory transmitter systems, such as the dopaminergic, 5-HT-ergic, acetylcholinergic, noradrenergic, and various neuropeptidergic systems, which control information processing in diencephalic and telencephalic regions of the brain (Castren, 2005;M€ uller et al, 2011). These systems display different modes of basal activity depending on various external factors and internal factors, such as glucose, oxygen, or hormone levels (M€ uller & Jacobs, 2010;Sarter, Hasselmo, Bruno, & Givens, 2005).…”

Episodic Memories and Their Relevance for Psychoactive Drug Use and Addiction

“…The acetylcholinergic (ACh) system plays an important role in attentional and memory processes (Blokland, 1995; Sarter et al, 2005) and is crucially involved in consciousness (Perry et al, 1999; Müller et al, 2011; Woolf and Butcher, 2011) and episodic memory (Dere et al, 2007). Acute application of cocaine was shown to activate cholinergic interneurons in the nucleus accumbens (Witten et al, 2010).…”