Inhibition by antibiotic tetracyclines of rat cortical noradrenergic adenylate cyclase and amphetamine-induced hyperactivity.
Two antibiotic tetracyclines, demeclocycline (DMC) and minocycline, share several biochemical and behavioral properties with lithium (Li). DMC inhibited both noradrenaline- and chloradenosine-sensitive cyclic AMP accumulation in rat cerebral cortical slices both in vitro and ex vivo following two weeks of chronic dietary treatment. Minocycline, a lipophilic tetracycline, produced similar results in vitro. Both DMC and minocycline reduced open-field activity levels in rats following acute treatment, four hours prior to testing. Moreover, both drugs inhibited amphetamine-induced hyperactivity in the open field. Chronic treatment with 0.4% and 0.8% dietary DMC for two weeks attenuated amphetamine hyperactivity without affecting baseline activity levels in the open field. Neither DMC nor minocycline attenuated apomorphine-induced stereotypy at doses that attenuated amphetamine hyperactivity, a profile which is similar to that of lithium. Unlike lithium, however, DMC did not reverse reserpine-induced hypoactivity.
Kofman
O
O
Beer Sheva Mental Health Centre, Ben Gurion University of the Negev, Israel.
Klein
E
E
Newman
M
M
Hamburger
R
R
Kimchi
O
O
Nir
T
T
Shimon
H
H
Belmaker
R H
RH
D015762:2-Chloroadenosine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D000242:Cyclic AMP / Q000378:metabolism; D003707:Demeclocycline / Q000494:pharmacology; D004032:Diet; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008911:Minocycline / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013754:Tetracyclines / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D013754:Tetracyclines; D015762:2-Chloroadenosine; D003707:Demeclocycline; D012110:Reserpine; D008094:Lithium; D000661:Amphetamine; D000242:Cyclic AMP; D008911:Minocycline; D009638:Norepinephrine