Psychostimulants

Abstract

Psychstimulants are a broadly defined class of drugs that stimulate the central and peripheral nervous systems as their primary pharmacological effect. The abuse liability of psychostimulants is well established and represents a significant public health concern. An extensive literature documents the critical importance of monoamines (dopamine, serotonin, and norepinephrine) in the behavioral pharmacology and addictive properties of psychostimulants. In particular, dopamine plays a primary role in the reinforcing effects of psychostimulants in animals and humans. However, there is a growing body of evidence that highlights complex interactions among additional neurotransmitter, neuroendocrine, and neuropeptide systems. Cortical glutamatergic systems provide important regulation of dopamine function, and inhibitory amino acid ?‐aminobutyric acid (GABA) systems can modulate basal dopamine and glutamate release. Psychostimulants also activate the hypothalamic‐pituitary axis and thereby engage neuroendocrine systems linked to stress reactivity. Finally, endogenous neuropeptide systems, including opioids and neurotensin, appear to play an important role in the neuropharmacology of psychostimulants. Repeated exposure to psychostimulants can lead to robust and enduring changes in neurobiological substrates and corresponding changes in sensitivity to acute drug effects on neurochemistry and behavior. It is important to emphasize that some neurobiological changes are not evident when drug administration is terminated but actually emerge during the period of drug withdrawal. Significant advances in the understanding of neurobiological mechanisms underlying psychostimulant abuse and dependence have guided pharmacological treatment strategies to improve clinical outcome. In particular, functional agonist treatments may be used effectively to stabilize neurochemistry and behavior. In addition, medications that target glutamatergic and GABAergic function are reasonable candidates that have received significant attention. However, additional clinical studies are required in order to identify safe and efficacious pharmacotherapies.

Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter

“…These drugs exert profound effects on mental function and behaviour and are implicated in drug abuse and addiction (Sulzer et al ., ; Han and Gu, ; Kelly, ; Sulzer, ). The behavioural effects associated with these agents are closely linked to enhanced dopaminergic activity (Howell and Kimmel, ; Howell et al ., ). More specifically, the rewarding and hyperlocomotor effects of AMPH are related to dopamine (DA) release in the nucleus accumbens (Sellings and Clarke, ), which activates DA receptors resulting in the behavioural effects associated with AMPH and related drugs (Kalix, ; Rothman and Baumann, ; Williams and Galli, ; Negus et al ., ; Banks et al ., ; Sulzer, ).…”