Effects of the Cognition-Enhancing Agent ABT-239 on Fetal Ethanol-Induced Deficits in Dentate Gyrus Synaptic Plasticity
| Autor: | Martina J. Rosenberg, Rafael K. Varaschin, Derek A. Hamilton, Katherine G. Akers, Daniel D. Savage |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Pyrrolidines Alcohol Drinking Offspring Long-Term Potentiation Neurotransmission Fetal Development Rats Sprague-Dawley Neuropharmacology Species Specificity Pregnancy Internal medicine medicine Animals Rats Long-Evans Nootropic Agents Benzofurans Pharmacology Ethanol Dentate gyrus Histaminergic Long-term potentiation Perforant path Electrophysiological Phenomena Rats medicine.anatomical_structure Endocrinology Maternal Exposure Prenatal Exposure Delayed Effects Dentate Gyrus Synaptic plasticity Molecular Medicine Female Histamine H3 receptor Psychology Neuroscience Histamine H3 Antagonists |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 334:191-198 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.109.165027 |
| Popis: | Prenatal ethanol exposure causes deficits in hippocampal synaptic plasticity and learning. At present, there are no clinically effective pharmacotherapeutic interventions for these deficits. In this study, we examined whether the cognition-enhancing agent 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl) benzonitrile (ABT-239), a histamine H(3) receptor antagonist, could ameliorate fetal ethanol-induced long-term potentiation (LTP) deficits. Long-Evans rat dams consumed a mean of 2.82 g/kg ethanol during a 4-h period each day. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, offspring litter size, and birth weights were not different between ethanol-consuming and control groups. A stimulating electrode was implanted in the entorhinal cortical perforant path, and a recording electrode was implanted in the dorsal dentate gyrus of urethane-anesthetized adult male offspring. Baseline input/output responses were not affected either by prenatal ethanol exposure or by 1 mg/kg ABT-239 administered 2 h before data collection. No differences were observed between prenatal treatment groups when a 10-tetanus train protocol was used to elicit LTP. However, LTP elicited by 3 tetanizing trains was markedly impaired by prenatal ethanol exposure compared with control. This fetal ethanol-induced LTP deficit was reversed by ABT-239. In contrast, ABT-239 did not enhance LTP in control offspring using the 3-tetanus train protocol. These results suggest that histamine H(3) receptor antagonists may have utility for treating fetal ethanol-associated synaptic plasticity and learning deficits. Furthermore, the differential effect of ABT-239 in fetal alcohol offspring compared with controls raises questions about the impact of fetal ethanol exposure on histaminergic modulation of excitatory neurotransmission in affected offspring. |
| Databáze: | OpenAIRE |
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