Pharmacology, biochemistry, and behavior
-
Pharmacol. Biochem. Behav. · Apr 2012
Role of peripheral and spinal 5-HT(3) receptors in development and maintenance of formalin-induced long-term secondary allodynia and hyperalgesia.
The role of peripheral and spinal 5-HT(3) receptors in formalin-induced secondary allodynia and hyperalgesia in rats was assessed. Formalin produced acute nociceptive behaviors (flinching and licking/lifting) followed by long-term secondary mechanical allodynia and hyperalgesia in both paws. In experiments where the test drug was anticipated to augment or antagonize the response, 0.5 or 1% formalin, respectively, was used for injection. ⋯ Spinal (30-300 nmol/rat), but not peripheral (300 nmol/paw), post-treatment (on day 6) with ondansetron reversed established formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Results suggest that a barrage of afferent input induced by 5-HT at peripheral 5-HT(3) receptors participates in the development of formalin-induced long-term secondary allodynia and hyperalgesia in the rat. In addition, our data suggest that spinal 5-HT(3) receptors play an important role during development and maintenance of these evoked long-term behaviors.
-
Pharmacol. Biochem. Behav. · Apr 2012
The selective metabotropic glutamate receptor 7 allosteric agonist AMN082 prevents reinstatement of extinguished ethanol-induced conditioned place preference in mice.
Alcohol dependence is considered a major public health problem in modern societies. The role for glutamatergic neurotransmission in the reinforcing effects of ethanol is becoming increasingly evident. Our previous findings have shown that in rats, the mGluR7 positive allosteric agonist AMN082, but not its allosteric antagonist MMPIP, prevented ethanol consumption and preference in the two-bottle choice paradigm. ⋯ In contrast, mGluR7 activation using AMN082 reduced ethanol-induced CPP reinstatement, an effect reversed by co-administration of MMPIP. Collectively, these results indicate, for the first time, that activation of the mGluR7 receptor is effective in reducing the reinstatement of conditioned rewarding effects of ethanol. Taken together, the efficacy of AMN082 on the various phases of alcohol-CPP could represent an interesting pharmacological approach and could open a new line of research for the development of therapies to reduce ethanol intake in patients.