title: Acute and residual effects in adolescent rats resulting from exposure to the novel synthetic cannabinoids AB-PINACA and AB-FUBINACA.
abstract: Synthetic cannabinoids (SCs) have rapidly proliferated as recreational drugs, and may present a substantial health risk to vulnerable populations. However, information on possible effects of long-term use is sparse. This study compared acute and residual effects of the popular indazole carboxamide SC compounds AB-PINACA and AB-FUBINACA in adolescent rats with ∆9-tetrahydrocannabinol (THC) and control treatments. Albino Wistar rats were injected (i.p.) with AB-PINACA or AB-FUBINACA every second day (beginning post-natal day (PND) 31), first at a low dose (0.2 mg/kg on 6 days) followed by a higher dose (1 mg/kg on a further 6 days). THC-treated rats received equivalent doses of 6 × 1 mg/kg and 6 × 5 mg/kg. During drug treatment, THC, AB-PINACA, and AB-FUBINACA decreased locomotor activity at high and low doses, increased anxiety-like behaviours and audible vocalisations, and reduced weight gain. Two weeks after dosing was completed, all cannabinoid pre-treated rats exhibited object recognition memory deficits. These were notably more severe in rats pre-treated with AB-FUBINACA. However, social interaction was reduced in the THC pre-treated group only. Six weeks post-dosing, plasma levels of cytokines interleukin (IL)-1α and IL-12 were reduced by AB-FUBINACA pre-treatment, while cerebellar endocannabinoids were reduced by THC and AB-PINACA pre-treatment. The acute effects of AB-PINACA and AB-FUBINACA were broadly similar to those of THC, suggesting that acute SC toxicity in humans may be modulated by dose factors, including inadvertent overdose and product contamination. However, some lasting residual effects of these different cannabinoid receptor agonists were subtly different, hinting at recruitment of different mechanisms of neuroadaptation.
authors.affiliation: 1 School of Psychology, The University of Sydney, NSW, Australia.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Kevin
authors.affiliation: 1 School of Psychology, The University of Sydney, NSW, Australia.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Wood
authors.affiliation: 1 School of Psychology, The University of Sydney, NSW, Australia.
authors.forename: Jordyn
authors.initials: J
authors.lastname: Stuart
authors.affiliation: 2 Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.affiliation: 3 School of Chemistry, The University of Sydney, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Moir
authors.affiliation: 3 School of Chemistry, The University of Sydney, NSW, Australia.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Banister
authors.affiliation: 3 School of Chemistry, The University of Sydney, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: 1 School of Psychology, The University of Sydney, NSW, Australia.
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000009:adverse effects; D002186:Cannabinoids / Q000009:adverse effects*; D013759:Dronabinol / Q000009:adverse effects; D063388:Endocannabinoids / Q000009:adverse effects; D013287:Illicit Drugs / Q000009:adverse effects; D007191:Indazoles / Q000009:adverse effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D063388:Endocannabinoids; D013287:Illicit Drugs; D007191:Indazoles; D043884:Receptor, Cannabinoid, CB1; C000599671:N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide; D013759:Dronabinol; D014633:Valine; C000615602:AB-FUBINACA
keywords: AB-FUBINACA; AB-PINACA; Cannabinoid; adolescent; behaviour; memory