The histamine H3 receptor as a therapeutic drug target for CNS disorders.

The histamine H3 receptor plays a regulatory role in the pre-synaptic release of histamine and other neurotransmitters, making it an attractive target for CNS indications including cognitive disorders, narcolepsy, ADHD and pain. As more and more H3 antagonists/H3 inverse agonists progress through the clinic, knowledge is gained to define the profile of the 'ideal' compound in terms of specificity, pharmacokinetic parameters and both duration and magnitude of receptor occupancy. Whether a single compound profile for the treatment of different disorders can be defined remains to be seen.

Effects of repeated dizocilpine treatment on adult rat behavior after neonatal lesions of the entorhinal cortex.

Disturbed cortical development is implicated in some psychiatric diseases, e.g. in schizophrenia.

Stimulation of the metabotropic glutamate 2/3 receptor attenuates social novelty discrimination deficits induced by neonatal phencyclidine treatment.

Rationale: Glutamatergic mechanisms are implicated in psychiatric disorders such as schizophrenia. Modulation of glutamatergic neurotransmission via stimulation of the metabotropic glutamate 2/3 receptors (mGluR2/3) has been shown to reverse a number of behavioral effects of NMDA receptor antagonists thus indicating potential antipsychotic activity of mGluR2/3 agonists.

Objectives: The present study aimed to evaluate the effects of LY-354740 (mGluR2/3 agonist) and LY-487379 (mGluR2 potentiator) on social novelty discrimination in male Wistar rats that were treated with PCP (10 mg/kg, s.

Deficient prepulse inhibition induced by selective breeding of rats can be restored by the dopamine D2 antagonist haloperidol.

Deficient sensorimotor gating, measured as prepulse inhibition (PPI) of startle, reflects disturbed information processing found in neuropsychiatric disorders. Examining the ability to selectively breed rats for high and low PPI, results showed significant differences of PPI scores within two generations. Comparing antipsychotics to restore PPI of the low group, haloperidol was shown more effective than clozapine.

Habituation deficits induced by metabotropic glutamate receptors 2/3 receptor blockade in mice: reversal by antipsychotic drugs.

Cortical metabotropic glutamate receptors (mGluRs) seem to be involved in habituation of simple stimulus-bound behaviors (e.g., habituation to acoustic startle or odor-elicited orienting response).