TY - JOUR
T1 - Pharmacological and behavioral effects of the synthetic cannabinoid akb48 in rats
AU - Bilel, Sabrine
AU - Tirri, Micaela
AU - Arfè, Raffaella
AU - Stopponi, Serena
AU - Soverchia, Laura
AU - Ciccocioppo, Roberto
AU - Frisoni, Paolo
AU - Strano Rossi, Sabina
AU - Miliano, Cristina
AU - De Giorgio, Fabio
AU - Serpelloni, Giovanni
AU - Fantinati, Anna
AU - De Luca, Maria Antonietta
AU - Neri, Margherita
AU - Marti, Matteo
PY - 2019
Y1 - 2019
N2 - AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the in vivo pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid.
AB - AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the in vivo pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid.
KW - AKB48
KW - AM251
KW - Cardiorespiratory changes
KW - Conditioned place preference (CPP)
KW - Microdialysis
KW - Prepulse inhibition (PPI)
KW - Sensorimotor responses
KW - Synthetic cannabinoids
KW - AKB48
KW - AM251
KW - Cardiorespiratory changes
KW - Conditioned place preference (CPP)
KW - Microdialysis
KW - Prepulse inhibition (PPI)
KW - Sensorimotor responses
KW - Synthetic cannabinoids
UR - http://hdl.handle.net/10807/147443
UR - https://www.frontiersin.org/journals/neuroscience#
U2 - 10.3389/fnins.2019.01163
DO - 10.3389/fnins.2019.01163
M3 - Article
SN - 1662-4548
VL - 13
SP - 1163-N/A
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
ER -