TY - JOUR
T1 - The intrahippocampal administration of the neurosteroid allopregnanolone blocks the audiogenic seizures induced by nicotine
AU - Martin-Garcia, Elena
AU - Pallares, Marc
PY - 2005/11/16
Y1 - 2005/11/16
N2 - Allopregnanolone (AlloP), GABAA positive modulator, has efficacy as anticonvulsant. In contrast, nicotine and pregnenolone sulfate (PregS) act as potent convulsants. The present study aims to evaluate whether a promnesic dose of PregS and/or an anxiolytic dose of AlloP administered in the hippocampus can affect the audiogenic seizures induced by nicotine administration. Rats were assigned at random to six groups that received two consecutive intrahippocampal (dorsal CA1) injections once a week during three consecutive weeks. First injection: nicotine (4.6 μg, 20 mM) or saline, second injection: PregS (5 ng, 24 μM), AlloP (0.2 μg, 1.26 μM) or saline. After the last injections, locomotor activity and audiogenic seizures were tested. AlloP decreased the horizontal and vertical activity, suggesting sedative effects. Nicotine induced behavioral convulsions and AlloP acted as an anticonvulsant. AlloP reversed the seizures induced by nicotine and decreased the audiogenic convulsions in comparison with the controls. PregS also reversed the nicotine-induced audiogenic seizures in the nicotine group but not in the control group. These results suggest that anticonvulsive effects of AlloP and PregS are mediated by different action mechanisms such as GABAA positive modulation, or negative modulatory action on neural nicotinic acetylcholine receptors. Even though several brain structures could be involved, these results highlight the important role played by hippocampal cholinergic and GABAergic activities, as well as neurosteroids, especially AlloP, in preventing convulsive behavior. © 2005 Elsevier B.V. All rights reserved.
AB - Allopregnanolone (AlloP), GABAA positive modulator, has efficacy as anticonvulsant. In contrast, nicotine and pregnenolone sulfate (PregS) act as potent convulsants. The present study aims to evaluate whether a promnesic dose of PregS and/or an anxiolytic dose of AlloP administered in the hippocampus can affect the audiogenic seizures induced by nicotine administration. Rats were assigned at random to six groups that received two consecutive intrahippocampal (dorsal CA1) injections once a week during three consecutive weeks. First injection: nicotine (4.6 μg, 20 mM) or saline, second injection: PregS (5 ng, 24 μM), AlloP (0.2 μg, 1.26 μM) or saline. After the last injections, locomotor activity and audiogenic seizures were tested. AlloP decreased the horizontal and vertical activity, suggesting sedative effects. Nicotine induced behavioral convulsions and AlloP acted as an anticonvulsant. AlloP reversed the seizures induced by nicotine and decreased the audiogenic convulsions in comparison with the controls. PregS also reversed the nicotine-induced audiogenic seizures in the nicotine group but not in the control group. These results suggest that anticonvulsive effects of AlloP and PregS are mediated by different action mechanisms such as GABAA positive modulation, or negative modulatory action on neural nicotinic acetylcholine receptors. Even though several brain structures could be involved, these results highlight the important role played by hippocampal cholinergic and GABAergic activities, as well as neurosteroids, especially AlloP, in preventing convulsive behavior. © 2005 Elsevier B.V. All rights reserved.
KW - Allopregnanolone
KW - Anticonvulsant activity
KW - Audiogenic seizure
KW - Hippocampus
KW - Neurosteroid
KW - Nicotine
KW - Pregnenolone sulfate
KW - Sedative effect
U2 - 10.1016/j.brainres.2005.09.020
DO - 10.1016/j.brainres.2005.09.020
M3 - Article
SN - 0006-8993
VL - 1062
SP - 144
EP - 150
JO - Brain Research
JF - Brain Research
ER -