Blockade of striatal 5-HT2 receptors produces retrograde amnesia in rats.

We have recently reported that intrastriatal administration of the serotonin (5-HT) releasing drug p-chloroamphetamine, and of 5-HT itself, produces a significant retention deficit of inhibitory avoidance. It is not known which of the 5-HT receptors are involved in the amnesic effect of serotonin. The present experiment was aimed at determining whether 5-HT2 receptors within the striatum are involved in memory consolidation.

Regional infusions of serotonin into the striatum and memory consolidation.

Lesions, temporal inactivation, electrical stimulation and administration of drugs that antagonize synaptic activity of the striatum lead to significant deficits of memory. Also, it has been shown that interruption of dopaminergic, GABAergic, or cholinergic activity in discrete areas of this structure is sufficient to disrupt cognitive functions. In spite of the known interactions among dopamine, GABA, acetylcholine, and serotonin, there is a notable scarcity of data germane to the participation of striatal serotonin in learning and memory.

Effects of pretraining intrastriatal administration of p-chloroamphetamine on inhibitory avoidance.

Pretraining systemic administration of p-chloroamphetamine (PCA) consistently produces retention deficits of inhibitory avoidance. This drug causes a widespread acute release of serotonin from cerebral neuronal terminals, but it is not known where in the brain PCA exerts its disruptive cognitive effects. The present experiment was aimed at determining whether the striatum is a site of action of this drug.

Enhanced inhibitory avoidance training protects against the amnesic effect of p-chloroamphetamine.

The contribution of acetylcholine (ACh) to memory processing is well documented, but it has been proposed that it is not necessary for memory consolidation after an enhanced learning experience. It has been suggested that serotonin (5-HT) interacts with ACh during memory consolidation, although the nature of this interaction is unknown in the case of strong learning. As an initial approach to the study of these interactions, we determined whether training of inhibitory avoidance using relatively high aversive stimulation protects against the typical retention deficits produced by pre-training administration of the 5-HT releaser p-chloroamphetamine (PCA).