Behavioural pharmacology
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Behavioural pharmacology · Jun 2019
Inhibition of experimental visceral pain in rodents by cebranopadol.
The aim of this study was to investigate the efficacy of cebranopadol in two rodent models of visceral pain. Cebranopadol is a first-in-class analgesic with agonist activity at the nociceptin/orphanin FQ opioid peptide receptor and classical µ-, δ- and κ-opioid peptide receptors. Colitis was induced in Naval Medical Research Institute mice by intra-rectal infusion of mustard oil. ⋯ In rats with experimental pancreatitis, cebranopadol dose-dependently inhibited abdominal tactile allodynia (half-maximal effective dose, 0.13 µg/kg; 95% CI: 0.03-0.49). Behavioural manifestations of visceral pain were almost completely abolished at the highest doses tested in mice (17.2 µg/kg, intravenous) and rats (2.4 µg/kg, intravenous). We conclude that cebranopadol is a potent and effective antiallodynic and antihyperalgesic agent in rodent models of visceral pain.
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Behavioural pharmacology · Jun 2019
Punishment and reinforcement by opioid receptor agonists in a choice procedure in rats.
Intravenous (i.v.) drug self-administration remains the 'gold standard' for assessing abuse potential of drugs. Failure of a drug to maintain self-administration might indicate merely the absence of positive-reinforcing effects but might also indicate presence of aversive effects. Sensitivity to aversive effects is thought to affect the initiation and maintenance of drug use as well as relapse. ⋯ All rats predominantly chose a pellet alone when histamine+a pellet was the alternative, and they predominantly chose remifentanil+a pellet over a pellet alone. In experiment 2, spiradoline was punishing in rats with a history of histamine punishment but not drug-naive rats. This food choice procedure is sensitive to reinforcing and punishing effects of different drugs in the same subjects, suggesting that the procedure is well-suited for studying drug mixtures (e.g. μ and κ agonists) and the impact of different physiological conditions (e.g. pain) on reinforcement and punishment.