PIRACETAM AND ANIRACETAM ANTAGONISM OF CENTRALLY ACTIVE DRUG-INDUCED ANTINOCICEPTION

The effects of the nootropic drugs piracetam and aniracetam on antinoc iception induced by baclofen, bicuculline, and picrotoxin and on baclo fen-induced muscle relaxation were studied in mice. Antinociception wa s investigated using both the hot plate (thermal stimulus) and abdomin al constriction (chemical stimulus) tests. Both behaviour inhibition a nd muscle relaxation were observed by using the rota-rod test. Piracet am (30 mg/kg, IP) and aniracetam (10 mg/kg, PO) reduced baclofen, bicu culline, and picrotoxin antinociception without modifying analgesia in duced by non-GABAergic drugs such as morphine, physostigmine, clomipra mine, and diphenhydramine. In this concentration range, piracetam, and aniracetam were also able to reduce the inhibition of rota-rod perfor mance. At higher doses piracetam (100 mg/kg, IP) and aniracetam (100 m g/kg, PO) were able to completely prevent baclofen antinociception. Ho wever, when prevention of GABAergic antinociception was complete, pira cetam and aniracetam were able to block non-GABAergic antinociception also. Comparing the effects of piracetam and aniracetam with those exe rted by the GABA(B) antagonist CGP 35348, a reduction of non-GABAergic analgesia was also observed using higher doses of CGP 35348 (2.5 mu g per mouse ICV). The present results indicate that piracetam and anira cetam, by preventing both of the investigated effects of baclofen, hav e some selectivity against GABA(B)-mediated inhibition. The well-known activity of piracetam and aniracetam on learning and memory might, th erefore, depend, at least in part, on the removal of inhibitory GABA(B ) mechanisms that impair attention and cognitive functions.