Repeated treatment with 8-OH-DPAT induces tolerance to its ability to produce the 5-HT1A behavioural syndrome, but not to its ability to attenuate haloperidol-induced catalepsy.
When administered acutely, 5-hydroxytryptamine1A (5-HT1A) agonists attenuate the cataleptic side effects of antipsychotics. We investigated whether tolerance occurs to these effects after repeated administration of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). For comparison, we also assessed the ability of 8-OH-DPAT to produce elements of the 5-HT1A behavioural syndrome (i.e. forepaw treading, flat body posture and lower lip retraction), some of which readily demonstrate tolerance. Catalepsy was measured in rats using both the cross-legged position test and the bar test. Repeated treatment with 8-OH-DPAT (0.63-2.5 mg/kg subcutaneously), once daily for 4 days, did not significantly alter the ability of acute treatment with 8-OH-DPAT (0.01-2.5 mg/kg) to inhibit catalepsy induced by haloperidol (2.5 mg/kg) in either test. In contrast, the ability of 8-OH-DPAT to produce the 5-HT1A behavioural syndrome was significantly attenuated by the repeated treatment. The present data, showing an absence of tolerance to the anti-cataleptic effects of a 5-HT1A agonist, indicate that mixed dopamine antagonist/5-HT1A agonist compounds may continue to have a low propensity to induce extrapyramidal side effects during chronic treatment.
Prinssen
E P
EP
Centre de Recherche Pierre Fabre, Castres, France. eric.prinssen@pierre-fabre.com
Koek
W
W
Colpaert
F C
FC
Kleven
M S
MS
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D004195:Disease Models, Animal; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012559:Schizophrenia / Q000188:drug therapy; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013577:Syndrome
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol