Improved posttraumatic acquisition of a place learning task after repeated administration of a serotonergic agonist 8-OH-DPA

TY - ABST

T1 - Improved posttraumatic acquisition of a place learning task after repeated administration of a serotonergic agonist 8-OH-DPA

AU - Mala, Hana

AU - Mogensen, Jesper

N1 - Udgivelsesdato: september/oktober Volumne: 22

PY - 2008

Y1 - 2008

N2 - Introduction/ObjectivesStudies 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-HT1A 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 8th 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:Serotonergic agonists represent a new target for potential therapeutic strategies in the treatment of consequences after brain injury. In particular, 5-HT1A receptor agonists appear promising, and more research should be conducted in order to fully uncover the recovery enhancing potential of this class of drugs. 

AB - Introduction/ObjectivesStudies 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-HT1A 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 8th 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:Serotonergic agonists represent a new target for potential therapeutic strategies in the treatment of consequences after brain injury. In particular, 5-HT1A receptor agonists appear promising, and more research should be conducted in order to fully uncover the recovery enhancing potential of this class of drugs. 

M3 - Conference abstract in journal

SN - 1545-9683

VL - 22

SP - 575

JO - Neurorehabilitation and Neural Repair

JF - Neurorehabilitation and Neural Repair

IS - 5

T2 - 5th World Congress for NeuroRehabilitation

Y2 - 24 September 2008 through 27 September 2008

ER -