HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Reinforcing and discriminative stimulus effects of the neuroactive steroids pregnanolone and Co 8-7071 in rhesus monkeys.

AbstractRATIONALE AND OBJECTIVES:
The present study was designed to assess possible abuse-related effects of the endogenous neuroactive steroid pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and the orally bioavailable, water-soluble neuroactive steroid pro-drug Co 8-7071 (3alpha,21-dihydroxy-3beta-trifluoromethyl-5beta-pregnan-20- one, 21-hemisuccinate).
METHODS:
Four rhesus monkeys were prepared with chronic intravenous (i.v.) catheters and trained to press a lever under a ten-response fixed-ratio (FR) schedule of methohexital injection (0.1 mg/kg per injection). Three rhesus monkeys were trained to discriminate intragastric infusions of pentobarbital (10 mg/kg) from saline infusions under a FR5 schedule of stimulus-shock termination.
RESULTS:
At least two doses of pregnanolone (0.003-0.1 mg/kg per injection) maintained injections per session above saline levels in the four monkeys tested, whereas Co 8-7071 (0.01-1.0 mg/kg per injection) maintained injections per session above saline levels in two of four monkeys at relatively low levels of injections per session. In rhesus monkeys trained to discriminate pentobarbital, i.v. pregnanolone injections (0.1-1.7 mg/kg, 5-min presession) dose-dependently reproduced the discriminative stimulus effects of pentobarbital in all monkeys tested. Intravenous administration of Co 8-7071 (1-10 mg/kg, 5-min presession) resulted in a dose-dependent increase to >80% pentobarbital-appropriate responding in two of three monkeys tested. Following intragastric infusions of Co 8-7071 (1.0-30 mg/kg), > or =80% pentobarbital-appropriate responding occurred in one out of three monkeys at 10 mg/kg when administered 60 min before the session. When administered 120 min before the session, however, 10-30 mg/kg Co 8-7071 reproduced the discriminative stimulus effects of pentobarbital in each of the three monkeys tested.
CONCLUSIONS:
These data demonstrate barbiturate-like abuse-related effects that differed between two pregnane steroids. Whereas pregnanolone functioned as a reinforcer, suggesting that this compound has abuse potential, Co 8-7071 did not, despite having pentobarbital-like discriminative effects.
AuthorsJ K Rowlett, G Winger, R B Carter, P L Wood, J H Woods, W L Woolverton
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 145 Issue 2 Pg. 205-12 (Jul 1999) ISSN: 0033-3158 [Print] Germany
PMID10463322 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Co 8-7071
  • Prodrugs
  • Pregnanolone
Topics
  • Animals
  • Behavior, Animal (drug effects)
  • Discrimination Learning (drug effects)
  • Dose-Response Relationship, Drug
  • Female
  • Macaca mulatta
  • Male
  • Pregnanolone (administration & dosage, analogs & derivatives, pharmacology)
  • Prodrugs (pharmacology)
  • Reinforcement, Psychology
  • Self Administration

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: