The effects of serotonergic drugs on short-term spatial memory in rats

The effects of modulating the serotonergic system on short-term spatial memory were investigated using delayed matching to position and delayed non-matching to position procedures. Rats were trained on one of the two tasks until stability and then administered the drugs 30 min before a session. Fluoxetine (0.625-10 mg/kg), a serotonin uptake inhibitor, fenfluramine (0.313-5 mg/kg), a serotonin release enhancer, and ipsapirone (2.5-10 mg/kg), a serotonin 1A partial agonist, were all injected subcutaneously in saline solution. Apart from fenfluramine, none of the compounds affected accuracy in either procedure, but some effects on other non- mnemonic measures were seen. At 5 mg/kg, fenfluramine significantly affected latency to respond, total responses on the levers and nosepokes in the foodtray as well as accuracy, indicating a non-specific disruption of behaviour rather than a selective effect on memory processes. These data suggest that cognitive effects of serotonergic drugs are difficult to identify in normal animals, irrespective of the mechanism of action of the drug. These data conflict with recent reports indicating memory-enhancing effects of serotonin uptake inhibitors.