Table 1.

Effects of environmental factors on rodent models for the schizophrenia candidate gene neuregulin 1.

Nrg1 × Laboratory housing (i.e., minimal enrichment)
Transmembrane domain Nrg1 mutant male mice (Karl et al., 2007)	Minimal enrichment shifted the onset of the hyper-explorative and anxiogenic phenotype of Nrg1 mice to 3–4 months of age compared to mutant mice kept in standard laboratory housing (onset at 4–6 months of age).
Nrg1 × Stress
Acute restraint stress	No pronounced effect of Nrg1 on the endocrine and behavioral effects of acute restraint stress—only subtle, age-dependent modification of stress-induced corticosterone release and anxiety-like behaviors.
Transmembrane domain Nrg1 mutant male mice (Chesworth et al., 2012b)
Acute restraint stress	Altered habituation to an open field environment in Nrg1 mutant rats.
Adult Type II Nrg1 mutant rats (Taylor et al., 2011a,b)	Mutant Nrg1 resulted in increased baseline corticosterone levels and improved recovery of those levels post stress.
	Elevated baseline levels of glucocorticoid receptors in hippocampus and pituitary glands. Results are highly sex-specific.
Chronic variable stress	Female Nrg1 rats displayed no stress-induced reduction in corticosterone levels and showed increased extinction of cued fear conditioning (no such effects in male Nrg1 mutants).
Adolescent Type II Nrg1 mutant rats (Taylor et al., 2012)
Social defeat stress	Stress diminished hyper-locomotion and induced cognitive deficits in Nrg1 mutant mice without accompanying effects in control mice. Nrg1 mutant mice were protected against anhedonic properties of social defeat.
Transmembrane domain Nrg1 mutant mice (Desbonnet et al., 2012)
	The effects of stress on the cytokine response of mice were genotype-dependent (for details see study).
	Stress decreased interleukin-beta mRNA levels in the prefrontal cortex of Nrg1 mice. Striatal interleukin-beta levels were reduced in control mice and increased in Nrg1 mice. Hippocampal BDNF mRNA levels were elevated in control mice and reduced in mutant mice whereas tumor necrosis factor-alpha was up-regulated in Nrg1 mice only.
Nrg1 × Cannabis reviewed in (Arnold et al., 2012; Karl and Arnold, 2013; Ng et al., 2013)
Acute treatment with Δ 9-tetrahydrocannabinol (THC)	Nrg1 mutants displayed a sex-dependent increased susceptibility to the locomotion-suppressive effects of THC and showed improved prepulse inhibition post THC treatment.
Adult transmembrane domain Nrg1 mutant mice (Boucher et al., 2007a,b; Long et al., 2010)
	THC induced increased neuronal activity in the ventral part of the lateral septum and greater activity in central nucleus of the amygdala and the paraventricular nucleus of the hypothalamus in Nrg1 mutant mice.
Chronic treatment with CP55,940 (CP)	Nrg1 mutants developed a behavioral tolerance to CP-induced hypothermia and hypolocomotion more rapidly, whereas the same mice did not develop a tolerance to CPs anxiogenic effects.
Adult transmembrane domain Nrg1 mutant male mice (Boucher et al., 2011)
	Mutant mice showed a selectively increase in CP-induced FosB/Δ FosB expression in the ventral part of lateral septum.
Chronic THC treatment	THC exacerbated hyperlocomotion 48 h after THC withdrawal. Nrg1 mutant mice were more resistant to social withdrawal effects of THC.
Adolescent transmembrane domain Nrg1 mutant male mice (Long et al., 2013)
	THC promoted genotype-dependent effects on CB1, 5-HT2A and NMDA receptor expression (see study for details).