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Also, in 4 monkeys administrated with bisacodyl, 3 excreted antibiotic resistant infection

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feces. This suggests that a factor intrinsic to pindolol antagonises

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the behavioural effects of Paroxetine ( Paxil ) in the olfactory bulbectomised rat. However, the group treated with both Paroxetine ( Paxil ) and pindolol failed

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to reverse the hyperactive response.

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In this study, we investigate the effects of combining pindolol (2 mg/kg, s.c., bid) with the antidepressant Paroxetine ( Paxil ) (2.5 mg/kg, i.p., bid) in the olfactory bulbectomised rat, an animal model of chronic (but not acute) antidepressant activity. This model

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may also be useful for the evaluation of laxatives. Combining pindolol and Paroxetine ( Paxil ) in an animal model of chronic antidepressant action--can

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early onset of action be detected?The realisation that pindolol may accelerate the effects of some antidepressant drugs in clinical trials has added extra impetus to the search for faster acting antidepressants.

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However, an animal model sensitive to the effects of any such compound and the actions of pindolol remains elusive.. Normal control monkeys excreted feces frequently

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throughout the day. We tested the appropriateness of this Amitriptyline ( Elavil )-induced constipated monkey model by observing the effects

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of a new laxative, the herbal medicine ND-10 and the commercially available laxative bisacodyl. On the other hand, 160 mg/kg treated monkeys died within 24 h after administration. Likewise, Paroxetine ( Paxil

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) alone reversed the olfactory bulbectomy-induced hyperactivity in the open field following 14 days of treatment only, this being the normal time of an 'antidepressant' response in this model. Control monkeys (those not receiving ND-10 or bisacodyl) treated with 60 mg/kg Amitriptyline ( Elavil ) did not excrete feces up to 32 h after Amitriptyline ( Elavil ) administration in 2 of 3 monkeys. The

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80 and 120 mg/kg treated monkeys did not excrete feces until 24 h from administration of Amitriptyline ( Elavil ), and also sho prolonged crouching and lethargy. Monkeys treated with Amitriptyline ( Elavil ) at doses of 10-40 mg/kg sho delays in feces excretion. In this study, we confirmed that constipation can be caused in cynomolgus monkeys by oral administration of Amitriptyline ( Elavil ). Further, we simultaneously study adaptive changes in 5-HT1A receptor function, utilising alterations in the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Pindolol in combination with Paroxetine ( Paxil ) attenuated the hypothermic effects of 8-OH-DPAT

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as early as 3 days with a full reversal evident following 7 days, whereas Paroxetine ( Paxil ) alone did so after 14 days only. However, all monkeys treated with one tablet of ND-10 excreted feces. We therefore felt that the optimal dose for creating constipation

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in the monkeys was 60 mg/kg.

Ambulation scores were measured in separate groups of rats, following 3, 7 and 14 days of treatment. The ability of the combination group to attenuate the hypothermic effects of 8-OH-DPAT much faster further emphasises the role of the 5-HT1A receptor in the mechanism of action of antidepressants and as a target for the development of faster acting antidepressants. In an attempt to create an animal model of constipation in monkeys, Amitriptyline ( Elavil ) was administered to cynomolgus monkeys at doses of 10-160 mg/kg body weight via a nasogastric tube.