Centrally administered aminoglycoside antibiotics antagonize naloxone-precipitated withdrawal in mice acutely dependent on morphine.
The effects of i.c.v. administration of several aminoglycoside antibiotics on naloxone-precipitated morphine withdrawal symptoms were evaluated in mice acutely dependent on morphine. Neomycin (10-40 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80-320 micrograms/mouse) produced a dose-dependent reduction of the number of precipitated jumps, forepaw tremors and head shakes. The order of potency of the aminoglycoside antibiotics on all withdrawal symptoms was neomycin > gentamicin > kanamycin, which is the same order that these drugs show as N-type calcium channel blockers. The capacity of several drugs that decrease neuronal calcium availability (such as lanthanum and L-type calcium channel blockers) to antagonize opiate withdrawal is well known. In the light of these findings, our results suggest that the mechanism of aminoglycoside-induced inhibition of morphine abstinence may be related to the capacity of these antibiotics to block N-type calcium channels, and to decrease neuronal calcium availability.
Robles
I
I
Department of Pharmacology, School of Medicine, University of Granada, Spain.
Barrios
M
M
Baeyens
J M
JM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005839:Gentamicins / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D007612:Kanamycin / Q000494:pharmacology; D051379:Mice; D009021:Morphine Dependence / Q000523:psychology*; D009270:Naloxone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009270:Naloxone; D007612:Kanamycin; D009355:Neomycin