Microdialysis and the neurochemistry of addiction

Abstract

Drug addiction is a process beginning with the initial exposure to a drug of abuse, and leading, in some individuals, to chronic habitual use, and high rates of relapse. Microdialysis allows researchers to monitor the neurochemical changes that occur in the brain after the initial exposure to a drug, and the neurochemical changes that occur with repeated exposure. These changes in the brain are often referred to as drug-induced neuroplasticity, and the aim of this article is to review studies that have utilized microdialysis to increase our understanding of the neuroplasticity that occurs in the process of addiction. We will review how several neurotransmitter systems, including glutamate, GABA, the monoamines, and others, are altered after chronic drug exposure, and how microdialysis can be used to determine if putative treatments for addiction can reverse the drug-induced neuroplasticity in these systems. We will also briefly discuss our recent research using a known change in GABA neurotransmission that occurs during reinstatement of drug-seeking to screen for possible novel treatments to prevent relapse. Overall, microdialysis in combination with other behavioral and pharmacological techniques has greatly increased our understanding of addiction related neuroplasticity, and provides a means for discovering new ways to prevent these changes and treat addiction.

The ins and outs of the striatum: Role in drug addiction

“…For example, microdialysis studies have shown increases in the concentration of these neurotransmitters within the striatum following both acute and chronic drug exposure as well as during relapse of drug-seeking behavior (Di Chiara and Imperato, 1988, Pierce et al, 1996, for review see Torregrossa and Kalivas, 2008). In addition, correlative studies utilizing immediate early gene expression as a marker of neuronal activation indicate the involvement of the striatum, together with its source regions of glutamate (prefrontal cortex [PFC], thalamus, amygdala and hippocampus) and dopamine (VTA and SNr), in addiction-related behaviors, including relapse and psychomotor sensitization (Table 2, Neisewander et al, 2000, Ciccocioppo et al, 2001, Ostrander et al, 2003, Kelley et al, 2005, Kufahl et al, 2009).…”

Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

“…Cerebral microdialysis (CMD) is one of few techniques that allow for quantification of metabolic substrates, neurotransmitters, peptides, and hormones (among other substances) in the living animal [2]. There are many applications for microdialysis in the neurosciences, including: (1) studies of neurotransmitter release (e.g., glutamate and GABA) that can help understand such diverse physiology as the neuroplasticity that occurs in the process of addiction [3], neurotransmitter release during exercise [4], and the neurotransmitter release associated with excitotoxicity in animal studies [5]; (2) pharmacodynamic studies [6]; (3) studies of drug metabolism, distribution, pharmacokinetics, and pharmacokineticpharmacodynamic (PK-PD) modeling; (4) pain research [7]; (5) studies of plasma protein binding and the saturation of protein binding; and (6) investigation of the therapeutic effect of medications on extracellular levels of substances involved in metabolism and neurotransmission (e.g., acetylcholine, catecholamines, serotonin, amino acids, peptides, glucose, lactate, glycerol, and hormones) [6]. Finally, reverse microdialysis is a powerful technique for studying local drug actions in different tissues like specific brain nuclei.…”

Neurotensin in the Ventral Pallidum Increases Extracellular γ-Aminobutyric Acid and Differentially Affects Cue- and Cocaine-Primed Reinstatement

“…Therefore, one strategy for preventing drug relapse is to increase GABAergic tone in the VP, countermanding the MOR-mediated disinhibition of VP output neurons produced by cocaine and thereby inhibiting reinstatement behavior. This was done previously by microinjecting GABA agonists into the VP (McFarland and Kalivas, 2001) but might also be accomplished by exploiting colocalized neuropeptides that positively regulate GABA release in the NAc projection to the VP (Torregrossa and Kalivas, 2007).…”