Effects of two 5-hydroxytryptamine agonists on head-weaving behaviour in streptozotocin-diabetic mice.

The potencies of 5-methoxy-N, N-dimethyltryptamine (central 5-hydroxytryptamine 1 receptor agonist) and 8-hydroxy-2-(di-n-propylamino) tetralin (central 5-hydroxytryptamine 1A receptor agonist) in eliciting head-weaving behaviour were studied in streptozotocin-diabetic mice and a group of control animals. Both drugs induced head-weaving behaviour in the streptozotocin-diabetic mice and control animals, but the potencies of these 5-hydroxytryptamine 1 agonists were reduced in the streptozotocin-diabetic mice. The numbers of head weaves elicited in the streptozotocin-diabetic and control animals by the two drugs were suppressed by pre-treatment with propranolol (5-hydroxytryptamine 1A receptor antagonist) and methysergide (5-hydroxytryptamine 1 and 2 receptor antagonist), but not by ketanserin (5-hydroxytryptamine 2 receptor antagonist), confirming the involvement of the 5-HT1A receptor. Pretreatment with nicotinamide before administering streptozotocin prevented streptozotocin-induced hyperglycaemia and restored the inhibition of head-weaving behaviour observed in streptozotocin-diabetic mice. Insulin injection, which partially prevented streptozotocin-induced hyperglycaemia, completely prevented reduction of the number of head weaves elicited by 5-methoxy-N, N-dimethyltryptamine in streptozotocin-diabetic mice. These results suggest that the reduced response to 5-HT1 agonists in streptozotocin-diabetic mice may be caused by the depletion of insulin.