The CB receptor agonist WIN 55,212-2 fails to elicit disruption of prepulse inhibition of the startle in Sprague-Dawley rats.
BACKGROUND
A growing evidentiary body indicates cannabinoid exposure is conducive to cognitive impairment and psychotic phenomena in vulnerable individuals. In this respect, recent studies have displayed controversial results on the ability of cannabinoids to elicit sensorimotor gating alterations and attentional filtering, whose disruption is a distinctive feature of psychosis.


OBJECTIVE
The goal of this study was to investigate the effects of acute, subchronic, and chronic treatment with the synthetic CB receptor agonist WIN 55,212-2 (WIN) on prepulse inhibition (PPI) of the acoustic startle reflex (ASR), a powerful paradigm for evaluation of sensorimotor gating.


METHODS
Different groups of adult Sprague-Dawley rats were treated with 0.5, 1, and 2 mg/kg WIN (i.p.) acutely, as well as for 7 days and 21 days. All animals underwent testing 40 min after the last treatment and their evaluation was compared with that of animals treated with vehicle. In a separate group, the effects of WIN withdrawal were also analyzed, 24 h after discontinuation of a 21-day treatment.


RESULTS
No variation in PPI was detected in any of the test groups when compared with controls, whatever the dosage and the treatment.


CONCLUSIONS
These findings suggest WIN does not impair sensorimotor gating in Sprague-Dawley rats and confirm clinical evidence according to which cannabis is an unlikely causative of psychosis among non-vulnerable individuals. Nonetheless, since in other studies the same compound was shown to induce PPI alterations in Wistar rats, our results are also suggestive that genetic differences might be critical for the development of cannabis-induced cognitive disorders.
Bortolato
Marco
M
Department of Neuroscience B.B. Brodie, Center of Excellence Neurobiology of Dependence, University of Cagliari, Cittadella Universitaria, S.S. 554 Km 4,500, 09042, Monserrato, CA, Italy. marco.bortolato@inwind.it
Aru
Gian Nicola
GN
Frau
Roberto
R
Orrù
Marco
M
Luckey
Grant Christopher
GC
Boi
Gianluca
G
Gessa
Gian Luigi
GL
D000818:Animals; D048588:Benzoxazines; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007274:Injections, Intraperitoneal; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009622:Noise; D011600:Psychopharmacology / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011931:Reactive Inhibition; D043884:Receptor, Cannabinoid, CB1 / Q000008:administration & dosage / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*
D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone