Introduction/Objectives

Studies have indicated that serotonergic agonists may act neuroprotectively against neurochemical and mechanical injury to the brain, and diminish the negative consequences of secondary tissue response to the initial insult. Little is known about the mechanisms of such effects. Likewise, it is presently uncertain to what extent serotonergic agonists can reduce the functional consequences of focal brain injury. In this study, we have addressed the neuroprotective potential of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), which is a serotonin agonist binding specifically to 5-HT_1A receptor subtypes. The effects were evaluated in terms of functional performance on an allocentric place learning task. 

Participants/Materials/Methods:

68 animals served as experimental subjects. Initially, the rats were divided into 6 experimental groups, three of which were subjected to bilateral transection of fimbria-fornix, rendering the hippocampus dysfunctional. The other three groups were given sham control surgery. Within both the lesioned, and sham-operated animals, respectively, one group was administered a single dose of saline following surgery (SAL), one group was given a single dose (5mg/kg/b.w.) of 8-OH-DPAT immediately after surgery (SINGLE TREATM), and one group was treated with daily administration of 8-OH-DPAT (5mg/kg/b.w.) for the six subsequent days (the first administration taking place immediately after surgery) (REPEATED TREATM). The acquisition of the water maze based place learning task started on the 8^th day after surgery and continued daily for the next 25 days.

Results:

The results show that within the lesioned groups, the group that was subjected to repeated administration of 8-OH-DPAT (REPEAT TREATM) showed a significantly improved acquisition of the allocentric place learning task compared to the baseline lesion group (SAL). In contrast, the performance of the lesioned group that was given only a single administration of this agent (SINGLE TREATM) was not significantly different from that of the lesioned rats treated with saline. The performance of the sham-operated controls was unaffected by 8-OH-DPAT treatment.

Conclusion: