Behavioural evidence of agonist-like effect of isoteoline at 5-HT1B serotonergic receptors in mice

• DOI: 10.1111/j.2042-7158.2003.tb02442.x
• Publication Date: 2010-02-26T13:11:53Z
• Authors: Maria D Zhelyazko...; Delcho K Zhelyazkov
• Keywords: Male; Aporphines; 3. Good health; Mice; 03 medical and health sciences; 0302 clinical medicine; Escape Reaction; Receptors, Serotonin; Receptor, Serotonin, 5-HT1B; Animals; Infusions, Parenteral; Serotonin Antagonists; Social Behavior

AbstractIsoteoline is a compound of aporphine structure derived from the alkaloid glaucine. Previous studies with isoteoline have shown antagonistic activity at 5-HT2C serotonergic receptors. We have investigated whether isoteoline interacts with 5-HT1B receptors. An isolation-induced social behavioural deficit test in mice was used as a model of stimulation of these receptors. The deficit in the behaviour of isolated mice in this experimental procedure was reported to be sensitive to 5-HT1B-receptor stimulation, since agonists at these receptors are capable of reversing it. In our study, we used N-(3-trifluoromethylphenyl) piperazine (TFMPP) (2 mg kg−1) as a reference agonist at these receptor sites. TFMPP completely restored the normal behaviour of the isolated mice. Its effect was prevented by propranolol (4 mg kg−1), a β-adrenergic receptor antagonist with a high affinity for 5-HT1B receptors, which was inactive by itself. When isoteoline was given before TFMPP, it did not prevent the effect of the latter. Given alone at doses of 0.25, 1, 4 or 8 mg kg−1, isoteoline showed an effect of its own to normalize the behaviour of isolated mice. The effect of isoteoline (1 mg kg−1, i.p.) was antagonized by pretreatment with propranolol, indicating that it was mediated through stimulation of 5-HT1B receptors. Repeated treatment with isoteoline (1 mg kg−1, 2 × 3 days, i.p.) produced tolerance to its effect and significantly attenuated the effect of TFMPP, when animals were tested 16 h after the last injection. In conclusion, the results provided functional evidence of agonist-like activity of isoteoline at the 5-HT1B receptors.