Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

Abstract

Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role.

Daily morphine administration increases impulsivity in rats responding under a 5‐choice serial reaction time task

“…Opioid abusers tend to discount delayed rewards more rapidly than non‐users, often preferring small, immediately available, reinforcers over large reinforcers delivered after a delay (Madden et al, ). Moreover, studies in non‐human subjects such as rats and non‐human primates indicate that acute (Kieres et al, ; Pitts and Mckinney, ; Pattij et al, ) and repeated (Harvey‐Lewis et al, ; Schippers et al, ; Maguire et al, ; Maguire et al, ) administration of opioids such as morphine or heroin can increase choice of small immediately delivered reinforcers. Although there are some exceptions to the general relationship between opioid administration and discounting (see Harty et al, ; Eppolito et al, ; Maguire et al, ), studies to date support the view that increased delay discounting might be one consequence of repeated opioid use.…”

“…Moreover, studies in non‐human subjects such as rats and non‐human primates indicate that acute (Kieres et al, ; Pitts and Mckinney, ; Pattij et al, ) and repeated (Harvey‐Lewis et al, ; Schippers et al, ; Maguire et al, ; Maguire et al, ) administration of opioids such as morphine or heroin can increase choice of small immediately delivered reinforcers. Although there are some exceptions to the general relationship between opioid administration and discounting (see Harty et al, ; Eppolito et al, ; Maguire et al, ), studies to date support the view that increased delay discounting might be one consequence of repeated opioid use. Enhanced delay discounting could increase vulnerability for drug abuse insofar as it predisposes an individual to prefer the immediately available effects of drug‐taking rather than the delayed effects of remaining abstinent, such as improved health, additional income, and positive social interactions.…”

Effects of morphine/CP55940 mixtures on an impulsive choice task in rhesus monkeys

“…The monkeys were maintained at a healthy body weight by food received in sessions and in the home cage. Monkeys were previously trained to press levers for food pellets and had received drug injections (Maguire et al, 2016). The monkeys had not received any drug for at least 2 months prior to the current study.…”

“…Drugs were administered subcutaneously in a volume of 0.2 – 0.8 ml. Pretreatment times were 15 min for morphine and 60 min for CP55940; behavioral effects of morphine and CP55940 are apparent with 15 and 60 min, respectively, and last at least 90 min in various operant-conditioning tasks, including delay discounting (e.g., Maguire et al, 2012, 2013, 2016). All doses were expressed as the weight of the forms noted above.…”

“…Another possibility is that enhanced discounting might be a result of drug use. Acute administration of morphine can decrease preference for delayed versus immediate food reinforcers (i.e., increased discounting) in pigeons (Eppolito et al, 2013), rats (Kieres et al, 2004; Harvey-Lewis and Franklin, 2015), and rhesus monkeys (Maguire et al, 2016), and repeated administration of an opioid can increase delay discounting as well other forms of impulsivity, such as response inhibition (Verdejo-Garcia et al, 2007; Harvey-Lewis et al, 2012).…”