The antipsychotic aripiprazole induces antinociceptive effects: Possible role of peripheral dopamine D2 and serotonin 5-HT1A receptors.
Aripiprazole is an antipsychotic that acts by multiple mechanisms, including partial agonism at dopamine D2 and serotonin 5-HT1A receptors. Since these neurotransmitters also modulate pain and analgesia, we tested the hypothesis that systemic or local administration of aripiprazole induces antinociceptive responses. Systemic aripiprazole (0.1-10 mg/kg; i.p.) injection in mice inhibited formalin-induced paw licking and PGE2-induced hyperalgesia in the paw pressure test. This effect was mimicked by intra-plantar administration (12.5-100 µg/paw) in the ipsi, but not contralateral, paw. The peripheral action of aripiprazole (100 µg/paw) was reversed by haloperidol (0.1-10 µg/paw), suggesting the activation of dopamine receptors as a possible mechanism. Accordingly, quinpirole (25-100 µg/paw), a full agonist at D2/D3 receptors, also reduced nociceptive responses.. In line with the partial agoniztic activity of aripiprazole, low dose of this compound inhibited the effect of quinpirole (both at 25 µg/paw). Finally, peripheral administration of NAN-190 (0.1-10 μg/paw), a 5-HT1A antagonist, also prevented aripiprazole-induced antinociception. In conclusion, systemic or local administration of aripiprazole induces antinociceptive effects. Similar to its antipsychotic activity, the possible peripheral mechanism involves dopamine D2 and serotoninergic 5-HT1A receptors. Aripiprazole and other dopaminergic modulators should be further investigated as new treatments for certain types of pain.
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
Ana F
AF
Almeida-Santos
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
Renata C M
RC
Ferreira
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
Igor D
ID
Duarte
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
Daniele C
DC
Aguiar
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: thiromero@gmail.com.
Thiago R L
TR
Romero
Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: fabriciomoreira@icb.ufmg.br.
Fabricio A
FA
Moreira
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
D000700:Analgesics; D014150:Antipsychotic Agents; C000600618:DRD2 protein, mouse; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A; D000068180:Aripiprazole
Analgesia; Dopamine; Nociception; Partial agonist; Serotonin