RATIONALE: Tetracycline antibiotics share some neuroprotective and CNS effects with N-methyl- D-aspartate (NMDA) receptor antagonists. OBJECTIVES: 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.
RATIONALE: Tetracycline antibiotics share some neuroprotective and CNS effects with N-methyl- D-aspartate (NMDA) receptor antagonists. OBJECTIVES: 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.
Authors: Mehmet Sofuoglu; Marc Mooney; Thomas Kosten; Andrew Waters; Kenji Hashimoto Journal: Psychopharmacology (Berl) Date: 2010-09-14 Impact factor: 4.530