Evidence for positive allosteric modulation of cognitive-enhancing effects of nicotine by low-dose galantamine in rats.

Cognitive-enhancing effects of nicotinic acetylcholine receptor (nAChR) agonists may be of therapeutic potential in disease states characterized by nAChR hypofunction; however, effects tend to be of small magnitude and unlikely clinical significance. The co-administration of a nAChR positive allosteric modulator (PAM) may enable larger effects by potentiating nAChR responses to an agonist. The acetylcholinesterase (AChE) inhibitor galantamine is a nAChR PAM at a low dose range.

Prenatal kynurenine treatment in rats causes schizophrenia-like broad monitoring deficits in adulthood.

Rationale: Elevated brain kynurenic acid (KYNA) levels are implicated in the pathology and neurodevelopmental pathogenesis of schizophrenia. In rats, embryonic treatment with kynurenine (EKyn) causes elevated brain KYNA levels in adulthood and cognitive deficits reminiscent of schizophrenia.

Objectives: Growing evidence suggests that people with schizophrenia have a narrowed attentional focus, and we aimed at establishing whether these abnormalities may be related to KYNA dysregulation.