Dorsal and median raphe serotonergic system lesion does not alter the opiate withdrawal syndrome

Pharmacol Biochem Behav. 2002 Jul;72(4):979-86. doi: 10.1016/s0091-3057(02)00810-9.


Previous pharmacological studies have implicated serotonergic brain systems in opiate withdrawal. To test the hypothesis that serotonin (5-HT) has a critical role in the development of opiate withdrawal, we have employed a near-total brain 5-HT system lesion technique (90% depletion) using 5,7-dihydroxytryptamine combined with induction of opiate dependence by implantation of morphine pellets or by repeated injections of increasing doses of morphine. The effects of serotonergic neuron lesion were examined on spontaneous opiate withdrawal (changes in circadian locomotor activity) and naloxone-precipitated opiate withdrawal syndrome (the somatic aspect). The antiwithdrawal properties of clonidine, an alpha(2)-adrenoceptor agonist currently used for clinical treatment for the somatic signs of opiate withdrawal, were tested also in the lesioned rats. Our findings show that serotonergic lesions in morphine-dependent rats did not alter either the spontaneous or the naloxone-induced withdrawal syndrome (with exception of jumping behavior). Moreover, clonidine alleviated the naloxone-induced withdrawal syndrome in lesioned as well as in sham-operated morphine-dependent rats. These results demonstrate that 5-HT systems are not directly responsible for the development of the somatic opiate withdrawal syndrome in morphine-dependent rats.

Publication types

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

MeSH terms

  • 5,7-Dihydroxytryptamine / toxicity
  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Biogenic Amines / metabolism
  • Clonidine / pharmacology
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology
  • Morphine Dependence / psychology
  • Motor Activity / drug effects
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / adverse effects*
  • Opioid-Related Disorders / psychology
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / physiology*
  • Serotonin Agents / toxicity
  • Substance Withdrawal Syndrome / physiopathology
  • Substance Withdrawal Syndrome / psychology*
  • Weight Loss / drug effects


  • Adrenergic alpha-Agonists
  • Biogenic Amines
  • Narcotic Antagonists
  • Narcotics
  • Serotonin Agents
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Naloxone
  • Morphine
  • Clonidine