Behavioural effects of long term inhibition of 5-hydroxytryptamine receptors using metergoline

1. Rats were treated with acute and chronic schedules of metergoline (2.5 mg/kg I.P. twice daily) and acutely with dl-propranolol (15 mg/kg), amitriptyline (12.5 mg/kg) and fluoxetine (2 mg/kg). 2. Metergoline given both acutely and chronically blocked the behavioural response to the 5-hydroxytryptamine receptor agonist 5-methoxy-N1, N1-dimethyltryptamine (5MeODMT) (2.5 mg/kg I.P.). The response to 5MeODMT) was also blocked by acute administration of dl-propranolol and amitriptyline, but not fluoxetine. 3. Rats given chronic treatment with metergoline and then withdrawn from drug treatment for 3 days showed an enhanced response to 5MeODMT. 4. Chronic metergoline treatment caused an increase in ambulatory movement following 5MeODMT administration. 5. Exploratory behaviour, when measured under dark conditions, was reduced by chronic metergoline treatment. 6. The results suggest that supersensitivity to 5-hydroxytryptamine agonists can be induced by chronic treatment with an antagonist. Furthermore, metergoline and 5-methoxy-N1, N1-dimethyltryptamine may not act on identical receptor populations.