Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors

Prog Neurobiol. 2007 Feb;81(3):133-78. doi: 10.1016/j.pneurobio.2007.01.001. Epub 2007 Jan 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoreceptors / drug effects
  • Autoreceptors / metabolism
  • Brain / drug effects*
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Chemistry / drug effects*
  • Brain Chemistry / physiology
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacology*
  • Humans
  • Ligands
  • Receptor, Serotonin, 5-HT1A / drug effects*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin / metabolism
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / physiopathology
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Autoreceptors
  • Central Nervous System Stimulants
  • Ligands
  • Receptor, Serotonin, 5-HT1A
  • Serotonin