Hypoxia-induced cognitive deficits are mainly due to disturbances of the balance between the GABAergic and glutamatergic systems. Acquisition, consolidation and retention impairment in passive avoidance test, hypolocomotion in the open field test, an anxiogenic-like effect in the elevated plus-maze test and
hypothermia were observed in rats subjected to
hypoxia. Drugs which reduce
glutamate release may possess neuroprotective activity. Both, agonists of
GABA(B) (
baclofen) and group III mGlu receptors (L-AP4) influence the release of
glutamate. We studied the behavioral effects of
baclofen on
hypoxia-induced
amnesia and the role of
L-AP4 in these processes.
Baclofen impaired acquisition, produced an anxiogenic-like effect and lowered body temperature but reduced the
hypoxia-induced deficit of acquisition and consolidation of conditioned avoidance, diminished the anxiogenic-like effect, and reduced the motor inhibition produced by
hypoxia.
L-AP4 improved the acquisition, consolidation and retrieval processes as well as the
hypoxia-induced consolidation deficit in the passive avoidance test. Co-administration of
baclofen with
L-AP4 improved consolidation and enhanced the
baclofen activity vs. the respective group without
hypoxia. In a group of rats that had undergone
hypoxia, joint administration of
baclofen and
L-AP4 improved retrieval as well as enhanced the effect of
baclofen and
L-AP4 vs. their respective group without
hypoxia. The agonist of group III mGluRs did not change locomotor activity but diminished
baclofen-induced motility in rats without
hypoxia.
L-AP4 given alone or with
baclofen produced an anxiogenic-like effect in rats without
hypoxia but produced an
anxiolytic-like effect in those that had undergone
hypoxia.
L-AP4 did not influence the activity of
baclofen in the elevated plus-maze test.
L-AP4 given alone or with
baclofen did not
change body temperature. It is concluded that
baclofen and
L-AP4 may cooperate in the consolidation process in rats without
hypoxia and in retrieval of passive avoidance in animals that had undergone
hypoxia. The observed interaction is probably the result of activation of the
presynaptic receptors which influence
glutamate and
GABA release.