Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors.
Serotonin(1A)-receptors (5-HT(1A)-Rs) are important components of the 5-HT system in the brain. As somatodendritic autoreceptors they control the activity of 5-HT neurons, and, as postsynaptic receptors, the activity in terminal areas. Cocaine (COC), amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine ("Ecstasy", MDMA) are psychostimulant drugs that can lead to addiction-related behavior in humans and in animals. At the neurochemical level, these psychostimulant drugs interact with monoamine transporters and increase extracellular 5-HT, dopamine and noradrenalin activity in the brain. The increase in 5-HT, which, in addition to dopamine, is a core mechanism of action for drug addiction, hyperactivates 5-HT(1A)-Rs. Here, we first review the role of the various 5-HT(1A)-R populations in spontaneous behavior to provide a background to elucidate the contribution of the 5-HT(1A)-Rs to the organization of psychostimulant-induced addiction behavior. The progress achieved in this field shows the fundamental contribution of brain 5-HT(1A)-Rs to virtually all behaviors associated with psychostimulant addiction. Importantly, the contribution of pre- and postsynaptic 5-HT(1A)-Rs can be dissociated and frequently act in opposite directions. We conclude that 5-HT(1A)-autoreceptors mainly facilitate psychostimulant addiction-related behaviors by a limitation of the 5-HT response in terminal areas. Postsynaptic 5-HT(1A)-Rs, in contrast, predominantly inhibit the expression of various addiction-related behaviors directly. In addition, they may also influence the local 5-HT response by feedback mechanisms. The reviewed findings do not only show a crucial role of 5-HT(1A)-Rs in the control of brain 5-HT activity and spontaneous behavior, but also their complex role in the regulation of the psychostimulant-induced 5-HT response and subsequent addiction-related behaviors.
Müller
Christian P
CP
Institute of Physiological Psychology I, University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany. muellercr@uni-duesseldorf.de
Carey
Robert J
RJ
Huston
Joseph P
JP
De Souza Silva
Maria A
MA
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D017660:Autoreceptors; D000697:Central Nervous System Stimulants; D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin