Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure

Neuropsychopharmacology. 2002 Sep;27(3):410-20. doi: 10.1016/S0893-133X(02)00306-8.


Acetyl-L-carnitine (ALCAR) is the acetyl ester of carnitine that has been reported to be beneficial in depressive disorders and Alzheimer's disease. A 7-day administration of ALCAR in rats increased dopamine and serotonin output in the nucleus accumbens shell and it prevented the development of escape deficit produced by acute exposure to unavoidable stress. No tolerance developed to this protective effect, which appeared to be mediated by (1) the activation of 5-HT(1A) receptors, as it was antagonized by the administration of WAY100635 30 min before stress exposure; and (2) a process of neuronal plasticity dependent on NMDA receptor activity, as subcutaneous dizocilpine infusion during ALCAR treatment prevented the development of the protective effect on stress. Chronic stress exposure maintains an escape deficit condition that is reverted by a long-term treatment with antidepressants, but the same condition was not modified by long-term ALCAR administration. Thus, ALCAR cannot be defined as an antidepressant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / pharmacology*
  • Analysis of Variance
  • Animals
  • Benzazepines / pharmacology
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism*
  • Dopamine Antagonists / pharmacology
  • Escape Reaction / drug effects
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Muscarinic Antagonists / pharmacology
  • Neuroprotective Agents / pharmacology
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Pain Threshold / drug effects
  • Piperazines / pharmacology
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Scopolamine / pharmacology
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Stress, Physiological / prevention & control
  • Time Factors


  • Benzazepines
  • Dopamine Antagonists
  • Muscarinic Antagonists
  • Neuroprotective Agents
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin
  • Acetylcarnitine
  • Dizocilpine Maleate
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Scopolamine
  • Dopamine