Repeated cocaine administration decreases 5-HT 2A receptor-Mediated serotonergic enhancement of synaptic activity in rat medial prefrontal cortex

Chiung Chun Huang, Ying Ching Liang, Cheng Che Lee, Mei Ying Wu, Kuei Sen Hsu

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Neural adaptations in the medial prefrontal cortex (mPFC) are thought to be crucial in the development and maintenance of addictive behaviors. The mPFC receives a dense serotonergic (5-hydroxytryptamine, 5-HT) innervation from raphe nuclei and 5-HT exerts complex actions on mPFC pyramidal neurons. The present study, using a rat model of behavioral sensitization to cocaine, was designed to determine whether repeated cocaine exposure in vivo is capable of altering 5-HT-induced regulation of glutamatergic transmission in the mPFC. In layer V pyramidal neurons of the mPFC, application of 5-HT, through activation of 5-HT 2A receptors, induced a massive enhancement of spontaneous excitatory postsynaptic currents (sEPSCs). Repeated cocaine administration for 5 days resulted in an attenuation in the ability of 5-HT to enhance sEPSCs. This effect was prevented when cocaine was co-administered with the selective 5-HT 2A receptor antagonist ketanserin and was mimicked by repeated 5-HT 2A receptor agonist (-)4-iodo-2,5-dimethoxyphenylisopropylamine administration. Repeated cocaine administration is not associated with any changes in the levels of 5-HT 2A receptors or regulator of GTP-binding protein signaling 4. These results suggest that cocaine-induced inhibition of 5-HT 2A receptor-mediated enhancement of glutamatergic transmission in the mPFC may be caused, at least in part, by the impairment of coupling of 5-HT 2A receptors with GTP-binding proteins during cocaine withdrawal. These alterations in 5-HT 2A receptor responsiveness in the mPFC may be relevant to the development of behavioral sensitization and withdrawal effects following repeated cocaine administration.

Original languageEnglish
Pages (from-to)1979-1992
Number of pages14
JournalNeuropsychopharmacology
Volume34
Issue number8
DOIs
Publication statusPublished - 2009 Jul

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

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