Withdrawal from continuous or intermittent cocaine: effects of NAN-190 on cocaine-induced locomotion.
Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regimen for 7 days. In Experiment 1, rats received 0- to 2.0-mg/kg IP injections of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190), a putative 5-hydroxytryptamine1A (5-HT1A) receptor antagonist. In Experiment 2, rats received the same doses of NAN-190 in combination with a 15-mg/kg IP injection of cocaine. The results of Experiment 1 indicate that the continuous-infusion group demonstrated a dose-dependent suppression of locomotor behavior by single doses of NAN-190. NAN-190 had no consistent dose-dependent effect on the locomotor behavior of subjects in the other pretreatment groups. The results of Experiment 2 indicate that rats receiving intermittent, daily injections tended to exhibit behavior consistent with 5-HT1A receptor supersensitivity. In contrast, rats receiving continuous cocaine tended to exhibit behavior consistent with 5-HT1A receptor subsensitivity. Changes in 5-HT1A receptor sensitivity may contribute to some of the anxiety and depressive symptoms exhibited by human cocaine abusers.
King
G R
GR
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Joyner
C
C
Lee
T H
TH
Ellinwood
E H
EH
D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000503:physiopathology*
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D003042:Cocaine