Allosteric modulation of M1 muscarinic acetylcholine receptor internalization and subcellular trafficking.

Allosteric modulators are an attractive approach to achieve receptor subtype-selective targeting of G protein-coupled receptors. Benzyl quinolone carboxylic acid (BQCA) is an unprecedented example of a highly selective positive allosteric modulator of the M1 muscarinic acetylcholine receptor (mAChR). However, despite favorable pharmacological characteristics of BQCA in vitro and in vivo, there is limited evidence of the impact of allosteric modulation on receptor regulatory mechanisms such as β-arrestin recruitment or receptor internalization and endocytic trafficking.

Long-term behavioral and NMDA receptor effects of young-adult corticosterone treatment in BDNF heterozygous mice.

Psychiatric illnesses, such as schizophrenia, are most likely caused by an interaction between genetic predisposition and environmental factors, including stress during development. The neurotrophin, brain-derived neurotrophic factor (BDNF) has been implicated in this illness as BDNF levels are decreased in the brain of patients with schizophrenia. The aim of the present study was to assess the combined effect of reduced BDNF levels and postnatal stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone.

Effects of N-acetyl-cysteine treatment on glutathione depletion and a short-term spatial memory deficit in 2-cyclohexene-1-one-treated rats.

Glutathione (GSH) is the primary antioxidant in the body and is present in high levels in the brain. Levels of GSH and other antioxidants are significantly altered in major psychiatric illnesses, such as schizophrenia. Recent clinical trials have demonstrated that chronic treatment with N-acetyl-l-cysteine (NAC), a GSH precursor, improved symptoms in individuals with this illness.

The effect of 'two hit' neonatal and young-adult stress on dopaminergic modulation of prepulse inhibition and dopamine receptor density.

Background And Purpose: A combination of early neurodevelopmental insult(s) and young-adult stress exposure may be involved in the development of schizophrenia. We studied prepulse inhibition (PPI) regulation in rats after an early stress, maternal deprivation, combined with a later stress, simulated by chronic corticosterone treatment, and also determined whether changes in brain dopamine receptor density were involved.

Experimental Approach: Rats were subjected to either 24 h maternal deprivation on postnatal day 9, corticosterone treatment from 8 to 10 weeks of age, or both.

Combined neonatal stress and young-adult glucocorticoid stimulation in rats reduce BDNF expression in hippocampus: effects on learning and memory.

Epidemiological studies suggest that multiple developmental disruptions are involved in the etiology of psychiatric illnesses including schizophrenia. In addition, altered expression of brain-derived neurotrophic factor (BDNF) has been implicated in these illnesses. In the present study, we examined the combined long-term effect of an early stress, in the form of maternal deprivation, and a later stress, simulated by chronic young-adult treatment with the stress hormone, corticosterone, on BDNF expression in the hippocampus of rats.

Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats.

The development of schizophrenia may include an early neurodevelopmental stress component which increases vulnerability to later stressful life events, in combination leading to overt disease. We investigated the effect of an early stress, in the form of maternal deprivation, combined with a later stress, simulated by chronic periadolescent corticosterone treatment, on behaviour in rats. Acute treatment with apomorphine caused disruption of prepulse inhibition (PPI) in controls and in rats that had undergone either maternal deprivation or corticosterone treatment, but was surprisingly absent in rats that had undergone the combined early and late stress.