title: Inhibition of microglia in the basolateral amygdala enhanced morphine-induced antinociception: Possible role of GABAA receptors.
abstract: In clinical medicine, morphine is widely used to relieve many types of pain, but it has several side effects such as the development of tolerance and dependence. In order to decrease the side effects of morphine administration for the treatment of pain, the combination of minocycline as a glial inhibitor and morphine has been suggested in previous studies. It is important to understand which synaptic mechanisms are involved in the potentiative effect of minocycline on morphine antinociception. To this aim, male Wistar rats were bilaterally cannulated in the basolateral amygdala by srereotaxic instrument. A tail-flick apparatus was used to measure the pain threshold. The results revealed that intraperitoneal injection of morphine (2.5-7.5 mg/kg) induced antinociception. Intra-basolateral amygdala microinjection of minocycline (5-10 µg/rat) by itself had no effect on tail-flick latency, while the microinjection of the same doses of minocycline with an ineffective dose of morphine (5 mg/kg) induced antinociception. Intra-basolateral amygdala microinjection of different doses of muscimol (0.001-0.005 µg/rat) increased the minocycline-induced potentioation on morphine response in the tail-flick test. Intra-basolateral amygdala microinjection of muscimol by itself had no effect on tail-flick latency. On the other hand, intra-basolateral amygdala microinjection of bicuculline (0.01-0.1 µg/rat) inhibited minocycline-induced potentiation of morphine antinociception. It should be noted that intra-basolateral amygdala bicucculine by itself had no effect on tail-flick latency. It can thus be concluded that intra-basolateral amygdala minocycline potentiates morphine response in the tail-flick test. Moreover, basolateral amygdala GABAergic system may be involved in the minocycline-induced potentiation of morphine response via GABAA receptors.
authors: Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors: Nastaran
authors: N
authors: Kosarmadar
authors: Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors: Zahra
authors: Z
authors: Ghasemzadeh
authors: Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. Electronic address: rezayof@khayam.ut.ac.ir.
authors: Ameneh
authors: A
authors: Rezayof
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D011963:Receptors, GABA-A; D009020:Morphine
keywords: Basolateral amygdala; GABA(A) receptors; Minocycline; Minocycline hydrochloride (PubChem CID: 54685925); Morphine; Morphine sulfate (PubChem CID: 5464280); Muscimol (PubChem CID: 4266); Rat(s); Tail-flick test; bicuculline (PubChem CID: 10237)