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There is an urgent need to transform basic research discoveries into tools for treatment and prevention of mental illnesses. This article presents an overview of the National Institute of Mental Health (NIMH) programs and resources to address the challenges and opportunities in psychiatric drug development starting at the point of discovery through the early phases of translational research. We summarize NIMH and selected National Institutes of Health (NIH) efforts to stimulate translation of basic and clinical neuroscience findings into novel targets, models, compounds, and strategies for the development of innovative therapeutics for psychiatric disorders. Examples of collaborations and partnerships among NIMH/NIH, academia, and industry are highlighted.

There is an urgent need to transform basic research discoveries into tools for treatment and prevention of mental illnesses. This article presents an overview of the National Institute of Mental Health (NIMH) programs and resources to address the challenges and opportunities in psychiatric drug development starting at the point of discovery through the early phases of translational research. We summarize NIMH and selected National Institutes of Health (NIH) efforts to stimulate translation of basic and clinical neuroscience findings into novel targets, models, compounds, and strategies for the development of innovative therapeutics for psychiatric disorders. Examples of collaborations and partnerships between NIMH/NIH, academia, and industry are highlighted.

A calcium-binding protein (protein 10) having a molecular mass of 29 kDa and an isoelectric point of 5.3 was purified from guinea pig brain. The amino acid sequence of fragments from proteolytic digestion of protein 10 revealed an 86% sequence identity with a calcium-binding protein (calretinin) found in chicken retina. Polyclonal antibodies against protein 10 revealed a specific distribution of this protein within sensory neurons of auditory, visual, olfactory, nociceptive, and gustatory systems as well as other discrete neuronal circuits in rat and guinea pig brain, whereas no specific label was observed in any of several peripheral tissues examined.

A series of 10 experiments examined the effects of the adenosine agonist, N('6)-(L-phenylisopropyl)adenosine (L-PIA), its isomer, D-PIA, and two adenosine antagonists, caffeine and theophylline, on the acquisition of conditioned responses in rabbits. Extension of the nictitating membrane was classically conditioned to a tone and light stimulus presented for 800 msec before delivery of a 100-msec shock unconditioned stimulus to the skin over the paraorbital region of the head. L-PIA (5.0 umol/kg) retarded acquisition to the tone and light conditioned stimuli while D-PIA at doses of 5.0 and 10.0 umol/kg had no effect. A control experiment employing explicitly unpaired presentations of the tone, light, and shock stimuli indicated that the retardant effect of L-PIA was due to an action on associative learning. L-PIA did not affect the shock intensity threshold for eliciting the unconditioned response nor did it affect the amplitude of the elicited responses. However, L-PIA did produce a large and significant reduction in the ability of the tone conditioned stimulus to elicit conditioned response. Theophylline (50-200 umol/kg) and caffeine (3-100 umol/kg) did not affect acquisition. Caffeine (300 umol/kg) had an unreliable effect on acquisition in that it produced a small but significant enhancement of acquisition to the tone and light stimuli in one out of three experiments. Both theophylline (200 umol/kg) and caffeine (300 umol/kg) completely antagonized the retardant effect of L-PIA (5.0 umol/kg) on acquisition. In addition, while neither theophylline (200 umol/kg) nor caffeine (300 umol/kg) had any effect alone on the tone intensity threshold for eliciting conditioned responses, both of these drugs completely blocked the effects of L-PIA (5.0 umol/kg) on tone thresholds. It was concluded that L-PIA retarded the rate of associative learning by decreasing the excitatory properties of conditioned stimuli. Furthermore, this effect of L-PIA on associative learning was attributed to an action at adenosine receptors. These effects of L-PIA suggest that endogenous adenosine may act to modulate the rate of associative learning.