PHARMACOLOGY OF MEMORY: DRUGS ACTING UPON THE NEUROTRANSMITTER MECHANISMS INVOLVED IN MEMORY CONSOLIDATION

The most labile and most sensitive link in the chain of events that constitute the memory process is the phase of consolidation that follows after acquisition, by which memories are transformed, at a loss, from an unstable into a stable state. Therefore the pharmacology of consolidation has been better studied than that of the other phases of memory (acquisition, storage, retrieval). Pharmacological studies unveiled much information concerning the actual mechanism of consolidation. This involves excitatory glutamatergic and cholinergic muscarinic synapses in the amygdala, medial septum and hippocampus, inhibited by benziodiazepine-regulated GABA-A synapses and modulated by B-noradrenergic terminals. Other additional neutrotransmitter systems, possibly different in each structure, may also intervene. Peripheral hormones reflexly modulate these mechanisms. The amygdala, medial septum and hippocampus process different aspects or components of memories (spatial, aversive, etc.). The entorhinal cortex, which receives projections from these three structures, has a post-consolidational, presumably integrative function. The glutamatergic synapses involved in memory consolidation in the amygdala and hippocampus sustain this late role of the entorhinal cortex through the generation of relatively brief long-term potentiations.