A follow-up study: acute behavioural effects of Delta(9)-THC in female heterozygous neuregulin 1 transmembrane domain mutant mice.
BACKGROUND
Heavy cannabis use is linked with an increased risk for schizophrenia. We showed previously that male heterozygous neuregulin 1 transmembrane domain (Nrg1 HET) mice are more sensitive to some effects of the psychotropic cannabis constituent Delta(9)-tetrahydrocannabinol (THC). We report data from a follow-up study in female Nrg1 HET mice, investigating THC effects on behaviours with some relevance to schizophrenia.


METHODS
Mice were injected with THC (0, 5 or 10 mg/kg i.p.) 30 min before a test battery: open field, elevated plus maze, novel object recognition (set 1) or light-dark, social interaction (SI) and prepulse inhibition (PPI 1: variable interstimulus interval (ISI); set 2). Another set (set 3) was injected with the same doses of THC before a fixed interstimulus interval PPI test (PPI 2).


RESULTS
Female Nrg1 HETs displayed the hallmark increased locomotor activity at 5 months and anxiolytic-like behaviour in the open field at 3 and 5 months. THC decreased locomotor activity in both genotypes. THC selectively reduced some SI behaviours in WT mice. Baseline PPI was enhanced in mutants under a variable ISI, while THC had no effect on PPI using either protocol.


CONCLUSIONS
This study reports novel findings on the baseline PPI profile and resistance to THC-induced social withdrawal in female Nrg1 HET mice. This is the first description of THC effects in females of this mouse model and suggests that the transmembrane domain Nrg1 mutation does not appear to have a severe impact on the behavioural sensitivity to THC in female mice.
Long
Leonora E
LE
Schizophrenia Research Institute, 405 Liverpool St., Darlinghurst, NSW 2010, Australia. l.long@powmri.edu.au
Chesworth
Rose
R
Arnold
Jonathon C
JC
Karl
Tim
T
D000818:Animals; D004195:Disease Models, Animal; D013759:Dronabinol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D020890:Neuregulin-1 / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics; D012919:Social Behavior
D020890:Neuregulin-1; D013759:Dronabinol