Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition

  title={Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition},
  author={Robert S. Mansbach and Elizabeth W. Brooks and Mark A. Sanner and Stevin H. Zorn},
Abstract Recent evidence suggests that the dopamine D4 receptor may play a role in schizophrenia, and that the atypical properties of the antipsychotic clozapine may be attributable in part to its antagonistic actions at this receptor. In the present study, clozapine and three other compounds having D4 dopamine receptor antagonist properties were examined for their effectiveness in reducing losses in prepulse inhibition (PPI) induced in rats by the dopamine receptor agonist apomorphine… 

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Antipsychotics possessing agonist efficacy at 5-HT1A receptors exhibit diverse profiles against apomorphine-induced PPI deficits, depending on the balance between D2 and 5- HT1A activities, suggesting that they may display distinct activity on some aspects of gating deficits in schizophrenic patients.

Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through Dopamine D3 Receptor Blockade

Results indicate, for the first time, that buspirone, through its D3R antagonist activity, may be a useful tool for improving the treatment of cognitive deficits in schizophrenia.

Selective dopamine D4 receptor antagonists

Recent findings with new biological models and D4 selective agonists may help clarify the role of the D4 receptor in the aetiology of schizophrenia.

Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys

Data show, for the first time, that D4 DRs modulate the cognitive functions of the frontostriatal system.

Disruption of prepulse inhibition of the startle reflex by the preferential D3 agonist ropinirole in healthy males

Results suggest a role for the dopamine D3 receptor in the mediation of human PPI, although a contribution from ropinirole’s agonistic activity at the D2 receptor cannot be entirely excluded.

Dopamine D4 receptor stimulation contributes to novel object recognition: Relevance to cognitive impairment in schizophrenia

D4 receptor agonism has a beneficial effect on novel object recognition in sub-chronic PCP-treated rats and augments the cognitive enhancing efficacy of an atypical antipsychotic drug that lacks affinity for the D4 receptor, lurasidone.



Multiple serotonin receptor subtypes modulate prepulse inhibition of the startle response in rats

Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat.

The present findings suggest that the activation of D2 dopamine receptors is responsible for the loss of PPI in rats, and overactivity of D 2 dopamine receptors might also be a substrate for PPI deficits in schizophrenia.

Dopamine receptor pharmacology.

Dopamine receptors are the primary targets in the treatment of schizophrenia, Parkinson's disease, and Huntington's chorea, and are discussed in this review by Philip Seeman and Hubert Van Tol.

Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine

The cloning of a gene that encodes a dopamine receptor gene that has high homology to the human dopamine D2 and D3 receptor genes is reported, which suggests the existence of other types of dopamine receptors which are more sensitive to clozapine.

Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4.

  • P. Seeman
  • Psychology, Medicine
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1992
An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.

Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat.

  • R. MansbachM. Geyer
  • Psychology, Biology
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1989
It is demonstrated that putative noncompetitive NMDA antagonists disrupt sensorimotor gating in rats and suggested that their effects may provide a model of the deficits in sensory gating exhibited by schizophrenic patients.

Induction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity.

All of the compounds examined elevated FLI in the nucleus accumbens and medial striatum, indicating that potential antipsychotic activity is predicted most consistently on this basis.