The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats.
The effects of intrahippocampal administration of nicotine and the neurosteroids pregnenolone sulfate and allopregnanolone on acquiring the lever-press response and extinction in a Skinner box were examined using voluntary alcohol-drinking rats. A free-choice drinking procedure that implies early availability of the alcoholic solution (10% ethanol v/v+3% glucose w/v in distilled water) was used. Alcohol and control rats were deprived of food and assigned at random to six groups. Each group received two consecutive intrahippocampal (dorsal CA1) injections immediately after 1-h of drinking ethanol and before the free lever-press response shaping and extinction session. The groups were: saline-saline; saline-pregnenolone sulfate (5 ng, 24 microM); saline-allopregnanolone (0.2 microg, 1.26 microM); nicotine (4.6 microg, 20 mM)-saline; nicotine-pregnenolone sulfate; nicotine-allopregnanolone. Blood alcohol concentrations were assessed the day before conditioning. The combination of the oral self-administration of ethanol and the intrahippocampal injection of nicotine deteriorated the ability to acquire the lever-press response. This effect was neutralized by intrahippocampal pregnenolone sulfate (negative modulator of the GABA(A) receptor complex), and it was not affected by intrahippocampal allopregnanolone (positive GABA receptor complex A modulator). Pregnenolone sulfate and allopregnanolone had no effects per se on lever-press acquisition, neither in alcohol-drinking rats nor in controls. Alcohol consumption facilitated operant extinction just as anxiolytics that act as positive modulators of the GABA receptor complex A receptors do, possibly reducing the anxiety or aversion related to non-reinforcement. This effect was increased by intrahippocampal nicotine.
Martín-García
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E
Institut de Neurociències, Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Pallarès
M
M
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004347:Drug Interactions; D005108:Extinction, Psychological / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009538:Nicotine; D011284:Pregnenolone / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
C018370:pregnenolone sulfate; D009538:Nicotine; D011284:Pregnenolone