Morphine-induced anxiolytic-like effect in morphine-sensitized mice: involvement of ventral hippocampal nicotinic acetylcholine receptors.
In the present study, the effects of repeated intra-ventral hippocampal (intra-VH) microinjections of nicotinic acetylcholine receptor agonist or antagonist on morphine-induced anxiolytic-like behavior were investigated in morphine-sensitized mice using elevated plus-maze. Intraperitoneal (i.p.) administration of different doses of morphine (5, 7.5 and 10mg/kg) increased the percentage of open arm time (%OAT), open arm entries (%OAE), but not locomotor activity, indicating an anxiolytic-like response to morphine. The maximum response was obtained by 7.5mg/kg of the opioid. The anxiety-like behavior which was induced by a lower dose of morphine (5mg/kg) was significantly increased in mice that had previously received once daily injections of morphine (10 and 20mg/kg, i.p.) for 3 days. It should be considered that this treatment also increased locomotor activity in morphine-sensitized mice. Furthermore, the response to an ineffective dose of morphine (5mg/kg, i.p.) in the EPM was significantly increased in the animals that had previously received nicotine for 3 days (0.1, 0.3, 0.5 and 0.7 μg/mouse; intra-VH), 5 min prior to the injections of morphine (5mg/kg/day × 3 days; i.p.). On the other hand, the increase of morphine-induced anxiolytic-like effect in animals that had previously received the 3-day morphine (20mg/kg) was dose dependently suppressed by once daily injections of mecamylamine (0.5, 1 and 2 μg/mouse/day × 3 days; intra-VH). It is important to note that repeated intra-VH administrations of the same doses of nicotine or mecamylamine alone caused no significant change in morphine (5mg/kg)-induced anxiety-like parameters in the EPM. In conclusion, it seems that morphine sensitization affects the anxiety-like behavior in the EPM and the cholinergic system in the ventral hippocampus, via nicotinic receptors, may play an important role in this effect.
Department of Animal Biology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran, Iran. rezayof@khayam.ut.ac.ir
Ameneh
A
Rezayof
Sara
S
Assadpour
Sakineh
S
Alijanpour
D000818:Animals; D021461:Animals, Outbred Strains; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D059333:Central Nervous System Sensitization / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*
D014151:Anti-Anxiety Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine