Introduction Microdialysis is an in vivo technique which

Introduction Microdialysis is an in vivo-technique which allows continuous sampling of small molecular weight substances (such as neurotransmitters, metabolites and neuropeptides) from the extracellular space of different tissues or organs, e.g. brain, muscle or skin. While the implantation of the probe requires anesthesia, the experiment itself can be performed in awake and freely-moving animals. This feature makes the method a useful addition to the repertoire of the behavioural neuroscientist. In this review, we will describe the characteristics of microdialysis and then illustrate the use of the method in behavioural research. The main focus of the article is on d-biotin (ACh) and its role in motor activity, attention and cognition.
Factors influencing acetylcholine release The microdialysis technique is widely used in experimental neuropharmacology, both in basic neuroscience and in drug development (Darvesh et al., 2011). Various drug-induced behavioural changes have been studied, including catalepsy, convulsions, stereotyped or turning behaviour. Early work in behavioural research using the microdialysis technique mainly concerned classical neurotransmitters (catechol-amines, acetylcholine, amino acids) and effects of circadian rhythm, food intake and stress and has been summarized by Westerink (1995). In addition, microdialysis has been used in behavioural experiments with wheels, treadmills or swimming pools or in animals involved in feeding, memory tests, copulation or parturition. Usually, microdialysis experiments combined with behavioural tests were carried out in rodents such as rats and mice but there are also examples from experiments in monkeys (Kimmel et al., 2009). In the following, we will cite some examples with a focus on cholinergic systems and its role in motor activity, attention and cognition.
Applications of microdialysis in behavioural research
Conclusion Microdialysis in animal models is highly useful to study behavioural paradigms, and therefore, it was also used to study animal models of neurological and psychiatric disease. While we have mentioned some neurological disorders such as epilepsy, dysfunction in cortical cholinergic neurotransmission has also been observed in models of addiction (Deller and Sarter, 1998) as well as in neuropsychiatric disorders such as schizophrenia, aging and Alzheimer’ disease (Sarter, 1994, Sarter et al., 2005).
Introduction Acetylcholinesterase (AChE) is a crucial enzyme for termination of the neurotransmission by catalyzing the hydrolysis of the neurotransmitter acetylcholine (ACh) into acetate and choline. Inhibition of the AChE upon intoxication of organophosphorus compounds (OP; e.g. pesticides and nerve agents) leads to an accumulation of ACh in the synaptic cleft. This results in a cholinergic crisis by overstimulation of muscarinic (mAChRs) and nicotinic acetylcholine receptors (nAChRs). The latter ones are driven into a desensitized state, hence blocking the cholinergic neurotransmission which can lead to death due to respiratory failure (Holmstedt, 1959). Basic treatment of OP poisoning with atropine is efficient to counteract symptomatically the toxic effects at mAChRs, but has no therapeutic effect at nAChRs (McDonough and Shih, 2007). Oximes used to reactivate AChE like obidoxime or pralidoxime have only a limited therapeutic effect especially in case of poisoning by tabun or soman. Tabun-inhibited AChE is rather resistant towards reactivation by oximes and the soman-AChE complex undergoes a rapid dealkylation (so-called “aging”) within minutes which prevents reactivation by oximes (Worek et al., 2007, Worek et al., 2004). The nicotinic receptors are pentameric ion channels from which sixteen subunits have been identified (α1–α7, α9, α10, β1–β4, γ, δ, ε) in humans. The α1, β1, γ, δ and ε subunits are expressed in muscles, whereas the α2–α7, α9, α210 and β1–β4 subunits are expressed more widely and are commonly referred to as neuronal subunits (Albuquerque et al., 2009). In this investigation we use the term “nAChR” for the muscle-type nicotinic acetylcholine of Torpedo marmorata (α1–γ–α1–δ–β) which is closely related to the adult human nAChR (α1–ε–α1–δ–β) (Hurst et al., 2013).