Acetaminophen modulation of hydrocodone reward in rats

► Illicit abuse of analgesics containing hydrocodone and acetaminophen is on the rise. ► Hydrocodone produced CPP in rats, whereas acetaminophen was devoid of such effect. ► When combined, acetaminophen enhanced hydrocodone CPP in a dose specific manner. ► Hydrocodone caused locomotor activity. ► When combined, acetaminophen did not enhance hydrocodone-induced locomotion.