title: Working memory- and anxiety-related behavioral effects of repeated nicotine as a stressor: the role of cannabinoid receptors.
abstract: BACKGROUND
  Like emotional symptoms such as anxiety, modulations in working memory are among the frequently-reported but controversial psychiatric symptoms associated with nicotine (NC) administration. In the present study, repeated NC-induced modulations in working memory, along with concurrently-observed anxiety-related behavioral alterations, were investigated in mice, and compared with the effects of a typical cognition-impairing stressor, immobilization stress (IM). Furthermore, considering the structural and functional contributions of brain cannabinoid (CB) receptors in NC-induced psychiatric symptoms including emotional symptoms, the interactive effects of brain CB receptor ligands (CB ligands) and NC and/or IM on the working memory- and anxiety-related behaviors were examined.
  
  
  RESULTS
  Statistically significant working memory impairment-like behavioral alterations in the Y-maze test and anxiety-like behavioral alterations in the elevated plus-maze (EPM) test were observed in the groups of mice treated with 0.8 mg/kg NC (subcutaneous (s.c.) 0.8 mg/kg treatment, 4 days) and/or IM (10 min treatment, 4 days). In the group of mice treated with NC plus IM (NC-IM group), an enhancement of the behavioral alterations was observed. Among the CB type 1 (CB1) antagonist AM 251 (AM), the non-selective CB agonist CP 55,940 (CP), and the CB1 partial agonist/antagonist virodhamine (VD), significant recovering effects were provided by AM (0.2-2.5 mg/kg) and VD (5 mg/kg) against the working memory impairment-like behaviors, whereas significant anxiolytic-like effects (recoveries from both attenuated percentage of entries into open arms and attenuated percentage of time spent on open arms) were provided by VD (1-10 mg/kg) and CP (2 mg/kg) against the anxiety-like behaviors.
  
  
  CONCLUSIONS
  Although working memory impairment- and anxiety-like behavioral alterations were commonly induced in the NC, IM, and NC-IM groups and the therapeutic involvement of CB receptors was shown, there were discrepancies in the types of effective CB ligands between the working memory- and anxiety-related behaviors. The differential involvements of CB receptor subtypes and indirectly activated neurotransmitter systems may contribute to these discrepancies.
authors: Department of Legal Medicine, Kyoto University, Yoshidakonoe-cho, Kyoto 606-8501, Japan. thayase@mri.biglobe.ne.jp
authors: Tamaki
authors: T
authors: Hayase
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy; D008570:Memory, Short-Term / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009538:Nicotine / Q000009:adverse effects*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D012149:Restraint, Physical / Q000009:adverse effects
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C103505:AM 251; D009538:Nicotine
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