Pain, 31 (1987) 263-276 Elsevier 263 PA1 01117 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Behavioural effects of receptor-specific substance P agonists Dalia Papir-Kricheli * , Joseph Frey *, Ralph Laufer *, Chaim Gilon * * , Michael Chorev * * *, Zvi Selinger * and Marshall Devor * * Life Sciences Institute, * * Institute of Chemistry, and * * * School of Pharmacy, Hebrew University of Jerusalem, Jerusalem 91904 (Israel) (Received 16 December 1986, revised received and accepted 30 April 1987) zyxwvutsrqponmlkji Sum m a ry Septide and senktide are synthetic substance P (SP) agonists with extremely high selectivity for 1 of the 3 known SP receptor subtypes. When injected intrathecally, they produced dramatically different behavioural effects. Septide, the selective SP-P receptor agonist, evoked intense, compulsive scratching, biting and licking of the hind limb, with no sign of motor flaccidity, and without measurable effect on responses to noxious thermal or mechanical stimulation of the foot or tail. In contrast, senktide, the selective SP-N receptor agonist, produced profound, but transient, motor flaccid- ity, reduced response to noxious stimuli and, at low doses, ‘wet-dog shakes.’ These various symptoms, all previously associated with SP and/or synthetic SP analogues, appear therefore to derive from activation of distinct SP receptor subtypes. Key words: Paralysis; Pain; Senktide; Septide; Substance P; Substance P receptor; Tachykinin; Tachykinin receptor zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Introduction Intrathecal injection of substance P (SP) and synthetic SP analogues in rodents produces a bizarre combination of behavioral symptoms [1,3-7,9,10,18,20-22,24, 27-29,31,32,34,35,39,43]. On the one hand, they produce hypersensitivity to noxious mechanical and thermal stimuli immediately upon drug injection, and a constella- tion of positive signs such as distress vocalization, ‘wet dog shakes,’ and compulsive scratching, biting and licking of the relevant body part. These effects have been taken to indicate that the animal is feeling discomfort or pain and are therefore widely quoted as supporting the candidacy of SP as a neurotransmitter in the pain Correspondence to: Dr. M. Devor, Life Sciences Institute, Hebrew University of Jerusalem, Jerusalem 91904, Israel. 0304-3959/87/$03.50 0 1987 Elsevier Science Publishers B.V. (Biomedical Division)