The substance P (NK1) receptor antagonist (+/-)-CP-96,345 causes sedation and motor impairment in Swiss albino mice in the black-and-white box behavioral paradigm.
In order to test the suggested involvement of substance P (NK1) receptors in anxiety, the non-peptide NK1 antagonist (+/-)-CP-96,345 was tested in Swiss albino mice using the black-and-white box behavioral paradigm. Intraperitoneal (+/-)-CP-96,345 dose-dependently decreased the motor activity and the number of exploratory rearings in both the brightly lit and dark compartment as well as the transitions between the compartments, whereas it increased the latency of the initial movement into the dark compartment as well as the time spent in the light section. ED50 or ID50 values ranged from 1.9 to 3.6 mg/kg and Hill slopes from 1.4 to 5.0. (+/-)-CP-96,345 also produced rotatory behavior of no preferred lateralization as well as the Straub phenomenon in some animals. The effects of (+/-)-CP-96,345 (5 mg/kg) were not affected by 2 mg/kg naloxone (i.p.) which was also ineffective when given alone. Thus, (+/-)-CP-96,345 does not display any anxiogenic effect but causes dose-dependent sedation and motor impairment.
D000818:Animals; D001007:Anxiety; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003864:Depression, Chemical; D005106:Exploratory Behavior / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors* / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D012399:Rotation; D013373:Substance P / Q000502:physiology*
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D013373:Substance P; D009270:Naloxone; C066892:CP 96345