Multiple 5-HT receptors in passive avoidance: comparative studies of p-chloroamphetamine and 8-OH-DPAT

Neuropsychopharmacology. 2000 Feb;22(2):168-90. doi: 10.1016/S0893-133X(99)00109-8.


The aim of this study was to examine the involvement of multiple 5-HT receptors in passive avoidance (PA) with a focus on 5-HT1A, 5-HT2A, and 5-HT2C receptors. Because increases in 5-HT transmission result in concomitant multiple 5-HT receptor activation, the effects of the 5-HT releasing compound p-chloroamphetamine (PCA) were compared with those of the selective 5-HT1A receptor agonist 8-OH-DPAT in the rat. In addition, some results with the nonselective 5-HT2C/2B/1B receptor agonist mCPP are presented. When injected before PA training, 8-OH-DPAT, mCPP, and PCA produced a dose-related impairment of the 24-hour retention. The crucial involvement of the postsynaptic 5-HT1A receptors in the action of 8-OH-DPAT was confirmed. Thus, the 5-HT1A receptor antagonists WAY 100635 and (-)-pindolol blocked the PA deficit by 8-OH-DPAT. The impairment of PA caused by PCA was attenuated by WAY 100635 and (-)-pindolol, suggesting an involvement of the 5-HT1A receptor. In contrast, the 5-HT2A and 5-HT2C receptors were of negligible importance in the 24-hour retention deficit induced by PCA. However, the ability of the 5-HT2C receptor antagonist Ro 60-0491 to block the inhibitory effects of mCPP indicated an important regulatory role of the 5-HT2C receptor in PA. The nonselective 5-HT receptor antagonist methiothepin attenuated the PA deficit by PCA but lacked activity versus 8-OH-DPAT. These data provide evidence for the hypothesis that, in addition to the 5-HT1A receptor, other 5-HT receptor subtypes are involved in the inhibitory actions of PCA. Importantly, changes in dopamine transmission seemed not to contribute to the PA impairment by PCA. The behavioral alterations caused by the drug treatments at the time of PA training could not be related to the subsequent retention performance. In conclusion, multiple 5-HT receptors are involved in PA with roles that probably differ at various stages of information processing. These findings also suggest that there probably exists a functional distinction between 5-HT receptor subtypes in different types of aversive learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Carrier Proteins / drug effects
  • Carrier Proteins / metabolism
  • Male
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Memory, Short-Term / drug effects
  • Memory, Short-Term / physiology
  • Nerve Tissue Proteins*
  • Pindolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists / pharmacology*
  • p-Chloroamphetamine / pharmacology*


  • Adrenergic beta-Antagonists
  • Carrier Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Receptor Agonists
  • Slc6a4 protein, rat
  • p-Chloroamphetamine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Pindolol