The neurosteroid pregnenolone sulfate neutralized the learning impairment induced by intrahippocampal nicotine in alcohol-drinking rats

E. Martín-García, M. Pallarès

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

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, 24μM); saline-allopregnanolone (0.2μg, 1.26μM); nicotine (4.6μg, 20mM)-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 GABAA 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. © 2005 Published by Elsevier Ltd on behalf of IBRO.
Original languageEnglish
Pages (from-to)1109-1119
JournalNeuroscience
Volume136
DOIs
Publication statusPublished - 1 Jan 2005

Keywords

  • Allopregnanolone
  • Chronic voluntary alcohol intake
  • Extinction
  • Hippocampus
  • Operant conditioning

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