Regulation of central synaptic transmission by 5-HT(1B) auto- and heteroreceptors

Mol Pharmacol. 2000 Dec;58(6):1271-8. doi: 10.1124/mol.58.6.1271.


Although 5-HT(1B) receptors are believed to be expressed on nerve terminals, their precise mode of action is not fully understood because of the lack of selective antagonists. The 5-HT(1B) receptor knockout mouse was used in the present investigation to assess the function of 5-HT(1B) receptors in the modulation of synaptic transmission in three areas of the central nervous system: the dorsal raphe, the ventral midbrain, and the nucleus accumbens. N-(3-Trifluoromethylphenyl)piperazine, a 5-HT(1B) receptor agonist, potently inhibited 5-HT(1A) receptor-mediated slow inhibitory postsynaptic potentials (IPSPs) in the dorsal raphe of wild-type but not knockout mice. Both synaptically released 5-HT and exogenous 5-HT caused a presynaptic inhibition that outlasted the postsynaptic hyperpolarization only in wild-type mice. In the ventral midbrain, 5-HT(1B) receptor-dependent inhibition of gamma-aminobutyric acid(B) IPSPs in dopamine neurons was present in wild-type animals and absent in knockout animals. Similar results were obtained in the nucleus accumbens measuring glutamate-mediated excitatory postsynaptic currents in medium spiny neurons. Finally, cocaine, which blocks 5-HT uptake, inhibited IPSPs in the dorsal raphe and the ventral midbrain of wild-type but not knockout mice, whereas cocaine produced comparable inhibition of excitatory postsynaptic currents in the nucleus accumbens of both types of animals. These results indicate that 5-HT(1B) receptors function as autoreceptors and heteroreceptors to exert presynaptic inhibition of transmitter release in the central nervous system. Furthermore, this study underscores the role played by presynaptic 5-HT(1B) receptors in mediating the effects of cocaine on synaptic transmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoreceptors / drug effects
  • Autoreceptors / physiology*
  • Cocaine / pharmacology
  • Dopamine Uptake Inhibitors / pharmacology
  • In Vitro Techniques
  • Mesencephalon / drug effects
  • Mesencephalon / physiology
  • Mice
  • Mice, Knockout
  • Neurons / drug effects
  • Neurons / physiology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Autoreceptors
  • Dopamine Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Cocaine