The anti-emetic action of the neurokinin(1) receptor antagonist CP-99,994 does not require the presence of the area postrema in the dog

Microinjection and ligand binding studies have implicated NK1 receptors in the area postrema (AP) in the emetic response to intragastric copper sulpha te that is mediated by abdominal vagal afferents. Because these afferents t erminate in the brainstem in the nucleus tractus solitarius in close proxim ity to the AP or in the AP itself, the results of such studies may be diffi cult to interpret. The present study has demonstrated in the dog that the e metic response to intragastric copper sulphate is unaffected by AP ablation , demonstrated functionally by absence of an emetic response to apomorphine (100 mug kg(-1) i.v.). In AP ablated animals the selective NK1 receptor an tagonist CP-99, 994 (1 mg kg(-1) im.) blocked the emetic response to copper sulphate as it did in intact animals. The results demonstrate that the AP is not involved in the blockade of the emetic response to intragastric copp er sulphate by an NK1 receptor antagonist and hence provides further suppor t for other sites proposed such as the nucleus tractus solitarius and centr al pattern generator. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.