Title: Arbi Nazarian, Ph'D'
1The Effects of Acetaminophen on the Rewarding
Properties of Hydrocodone in Rats
- Arbi Nazarian, Ph.D.
- Department of Pharmaceutical Sciences
- Western University of Health Sciences
- Pomona, CA
2Prescription Opioid Analgesics
- The Good
- Prescription opioid analgesics (e.g. Vicodin,
Oxycontin, Percodan) have been used for many
years for the treatment of moderate to severe
pain. - Quite a few of these analgesics are cocktail
formulations of 2 compounds an opioid agonist
(narcotic) , such as hydrocodone, oxycodone or
tramadol a non-narcotic analgesic, such as
acetaminophen, ibuprofen or aspirin. - Vicodin Hydrocodone Acetaminophen
- Percodan Oxycodone Aspirin
- Initial intent for the use of cocktail
formulations Reduce amount of narcotic, to
reduce risk of side effects, yet reach good
analgesic efficacy.
3Prescription Opioid Analgesics
- The Bad
- Use of Opioid analgesics can leads to complex
side effects - Respiratory Depression
- Constipation
- Analgesic Tolerance
- Physiological Dependence
- Psychological Dependence/Addiction
4Prescription Opioid Analgesics
- The Ugly
- Non-medical, illicit use of opioid analgesics is
on the rise. - In 2006, 5.2 million
- people in the U.S. used
- analgesics in a
- non-medical context.
- (NSDHU, 2007)
SAMHSA 2002
5Prescription Opioid Analgesics
- Most prevalent in adolescents and young adults.
(MTF, 2007)
6Cocktail formulation most commonly used in
nonmedical context
SAMHSA, 2002
7Why so much nonmedical use?
- Ease of access.
- Is that it?
- Can some cocktail formulations possess greater
rewarding effects than the opioid agonist alone?
8Could Hydrocodone Acetaminophen have greater
rewarding properties as compared to Hydrocodone,
alone?
- Experimental Approach
- Measure the rewarding effects of hydrocodone.
- Measure the rewarding effects of acetaminophen
- Measure the rewarding effects of hydrocodone
acetaminophen. - All experiments conducted in rats.
9How to measure drug reward in a rat?
- Conditioned place preference (CPP)
- Rats injected with drug or saline in a distinct
compartment over 4 conditioning, days. - Place preference
- measured on post-
- conditioning test day
- in a drug free state.
- CPP amount of time
- spent on the drug-
- paired side vs. saline-
- paired side.
10Results- Hydrocodone produced CPP in rats
11Results- Acetaminophen did not produce CPP in rats
12Results- Acetaminophen enhanced hydrocodone CPP
13Results- Acetaminophen did not enhance
hydrocodone-induced locomotor activity
Acute Locomotor Activity (Day 1)
Conditioned Locomotor Activity (Test Day)
14Summary
- Rats developed a CPP to hydrocodone (5.0 mg/kg).
- Rats did not develop a CPP to acetaminophen
- Rats developed a CPP to a combination of
acetaminophen and a non-CPP producing dose of
hydrocodone. - Acetaminophen did not enhance the locomotor
activating effects of hydrocodone
15Work in Progress
- Studying other doses of acetaminophen.
- Investigating potential mechanisms.
16Many Thanks
- Western University
- Deepthi Are
- Meagan Parker
- Yelba Carrillo
- Erika Estrada
- Consultant
- Dr. Kabir Lutfy
- Charles Drew University
- Dr. Theodore Friedman
- Funds Provided by
- Western University College of Pharmacy