Enhancement of the discriminative stimulus effects of phencyclidine by the tetracycline antibiotics doxycycline and minocycline in rats.
BACKGROUND
Tetracycline antibiotics share some neuroprotective and CNS effects with N-methyl- D-aspartate (NMDA) receptor antagonists.


OBJECTIVE
The acute effects of two tetracycline antibiotics were compared to those of the prototypic NMDA antagonist phencyclidine (PCP).


METHODS
The effects of minocycline (10-56 mg/kg) and doxycycline (10-56 mg/kg) were evaluated in Sprague-Dawley rats trained to discriminate 2.0 mg/kg IP of PCP from saline under a fixed ratio schedule of food presentation.


RESULTS
Even though minocycline and doxycycline did not substitute for PCP, pretreatment with 32 mg/kg of either drug produced leftward shifts in the PCP dose-response curve. The 32 mg/kg dose of minocycline also produced a leftward shift in the dose-response curve for dizocilpine (MK-801), another NMDA channel blocker, in the same subjects.


CONCLUSIONS
Tetracycline antibiotics may interact either directly or indirectly with NMDA receptors. This suggests that they might be utilized in treatment of brain disorders in which NMDA receptor over-activation has been implicated.
Munzar
Patrik
P
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298-0613, USA. pmunzar@hsc.vcu.edu
Li
Hua
H
Nicholson
Katherine L
KL
Wiley
Jenny L
JL
Balster
Robert L
RL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004318:Doxycycline / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D008911:Minocycline; D010622:Phencyclidine; D004318:Doxycycline