Get access

Dorsal hippocampal cannabinoid CB1 receptors mediate the interactive effects of nicotine and ethanol on passive avoidance learning in mice

Authors

  • Sakineh Alijanpour,

    1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Iran
    Search for more papers by this author
  • Ameneh Rezayof,

    Corresponding author
    1. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Iran
    Search for more papers by this author
  • Mohammad-Reza Zarrindast

    1. Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Iran
    2. Department of Pharmacology, School of Medicine and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Iran
    3. School of Cognitive Sciences, Institute for Research in Fundamental Sciences (IPM), Iran
    Search for more papers by this author

Ameneh Rezayof, Department of Animal Biology, School of Biology, College of Science, University of Tehran, P. O. Box: 4155-6455, Tehran, Iran. E-mail: rezayof@khayam.ut.ac.ir

ABSTRACT

The present study evaluated the involvement of the dorsal hippocampal cannabinoid CB1 receptors in the combined effect of ethanol and nicotine on passive avoidance learning in adult male mice. The results indicated that pre-training administration of ethanol (1 g/kg, i.p.) impaired memory retrieval. Pre-test administration of ethanol (0.5 and 1 g/kg, i.p.) or nicotine (0.5 and 0.7 mg/kg, s.c.) significantly reversed ethanol-induced amnesia, suggesting a functional interaction between ethanol and nicotine. Pre-test microinjection of a selective CB1 receptor agonist, ACPA (3 and 5 ng/mouse), plus an ineffective dose of ethanol (0.25 g/kg) or nicotine (0.3 mg/kg) improved memory retrieval, while ACPA by itself could not reverse ethanol-induced amnesia. Pre-test intra-CA1 microinjection of a selective CB1 receptor antagonist, AM251 (0.5–2 ng/mouse), did not lead to a significant change in ethanol-induced amnesia. However, pre-test intra-CA1 microinjection of AM251 prevented the ethanol (1 g/kg) or nicotine (0.7 mg/kg) response on ethanol-induced amnesia. In order to support the involvement of the dorsal hippocampal CB1 receptors in nicotine response, the scheduled mixed treatments of AM251 (0.1–1 ng/mouse), ACPA (5 ng/mouse) and nicotine (0.3 mg/kg) were used. The results indicated that AM251 reversed the response of ACPA to the interactive effects of nicotine and ethanol in passive avoidance learning. Furthermore, pre-test intra-CA1 microinjection of the same doses of ACPA or AM251 had no effect on memory retrieval. These findings show that the cannabinoid CB1 receptors of dorsal hippocampus are important in the combined effect of ethanol and nicotine on passive avoidance learning.

Ancillary