Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure.
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.
Tolu
Pierluigi
P
Department of Neuroscience, Pharmacology Unit, University of Siena, Siena, Italy.
Masi
Flavio
F
Leggio
Benedetta
B
Scheggi
Simona
S
Tagliamonte
Alessandro
A
De Montis
M Graziella
MG
Gambarana
Carla
C
D000108:Acetylcarnitine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013312:Stress, Physiological / Q000517:prevention & control; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D012701:Serotonin; D000108:Acetylcarnitine; D016291:Dizocilpine Maleate; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D012601:Scopolamine; D004298:Dopamine