“It has been suggested for some time that circadian rhythm abnormalities underlie the development of multiple psychiatric disorders. However, it is unclear how disruptions in individual circadian genes might regulate mood and anxiety. Here
we found that mice lacking functional mPeriod 1 (mPer1) or mPeriod 2 (mPer2) individually did not have consistent behavioral abnormalities in measures of anxiety-related behavior. However, mice deficient in both mPer1 and mPer2 had an increase in levels of anxiety-like behavior in multiple measures. Moreover, we found that mPer1 and mPer2 expression was reduced in the nucleus accumbens (NAc) after exposure to chronic social defeat stress, a paradigm that led to increased anxiety-related behavior. Following social defeat, chronic treatment with fluoxetine normalized Per gene expression towards wild-type levels. Knockdown of both mPer1 and mPer2 expression Z-VAD-FMK mouse via RNA interference specifically in the NAc led to a similar increase in anxiety-like behavior as seen in the mutant animals. Taken together, these results implicate the Per genes in the NAc in response to stress and the
development of anxiety. “
“Environmental contexts associated with drug use promote craving in humans and drug-seeking PLX3397 concentration in animals. We hypothesized that the basolateral amygdala (BLA) itself as well as serial connectivity between the BLA and nucleus accumbens core (NAC core) were required for context-induced renewal Tolmetin of Pavlovian-conditioned alcohol-seeking. Male Long-Evans rats were trained to discriminate between two conditioned stimuli (CS): a CS+ that was paired with ethanol (EtOH, 20%, v/v) delivery into a fluid port (0.2 mL/CS+, 3.2 mL per session) and a CS− that was not. Entries into the port during each CS were measured. Next, rats received extinction in a different context where both cues were presented without EtOH. At test, responding to the CS+ and CS− without EtOH was evaluated in the prior training context. Control subjects showed a selective increase in CS+ responding relative to extinction, indicative of renewal. This effect was blocked by pre-test, bilateral inactivation of the BLA using
a solution of GABA receptor agonists (0.1 mm muscimol and 1.0 mm baclofen; M/B; 0.3 μL per side). Renewal was also attenuated following unilateral injections of M/B into the BLA, combined with either M/B, the dopamine D1 receptor antagonist SCH 23390 (0.6 μg per side) or saline infusion in the contralateral NAC core. Hence, unilateral BLA inactivation was sufficient to disrupt renewal, highlighting a critical role for functional activity in the BLA in enabling the reinstatement of alcohol-seeking driven by an alcohol context. “
“Department of Biology, Eastern Washington University, Cheney, WA, USA Department of Biomedical Sciences, Grand Valley State University, Allendale, MI, USA Methamphetamine (METH) is a highly addictive drug that is also neurotoxic to central dopamine (DA) systems.