Role of serotonin-1A receptors in the action of antipsychotic drugs: comparison of prepulse inhibition studies in mice and rats and relevance for human pharmacology.
This study aimed to explore strain and species differences in the involvement of 5-HT1A receptors in the action of antipsychotic drugs, using prepulse inhibition (PPI), a model of sensory processing which is deficient in schizophrenia patients. We used automated startle boxes to compare the effect of the 5-HT1A receptor agonist, (+/-)-8-hydroxy-dipropyl-amino-tetralin (8-OH-DPAT), on PPI in three mouse strains. Balb/c mice were then pretreated with antipsychotics, treated with 8-OH-DPAT or saline, and tested for PPI. 8-OH-DPAT treatment dose dependently increased PPI in Balb/c mice, but had less effect in 129Sv and C57Bl/6 mice. In Balb/c mice, the effect of 8-OH-DPAT was blocked by the typical antipsychotic and dopamine D2 receptor antagonist, haloperidol and the third generation antipsychotic, aripiprazole, which has activity at both 5-HT1A and dopamine D2 receptors. The atypical antipsychotics, clozapine, olanzapine and risperidone, had lesser effects. Similar to our earlier studies in rats, the present PPI results suggest that 5-HT1A receptors are involved in the action of some antipsychotic drugs in mice. Despite strain and species differences in the magnitude and direction of the effect of 8-OH-DPAT, downstream dopamine D2 receptor activation seems to be an important mediator. These comparative results allow a theoretical framework of receptor interactions, which may guide further studies on the involvement of 5-HT1A receptors in schizophrenia.
Gogos
Andrea
A
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, Melbourne, Australia.
Bogeski
Mirjana
M
van den Buuse
Maarten
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D001569:Benzodiazepines; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000068180:Aripiprazole; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine