Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

Abstract

Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior.

Adolescent oxycodone self administration alters subsequent oxycodone-induced conditioned place preference and anti-nociceptive effect in C57BL/6J mice in adulthood

“…This was compared to a group that underwent the same protocol, but with the initial oxycodone self-administration sessions occurring in adulthood. As mentioned above, testing in the CPP and antinociception endpoints occurred 14 days after the end of the oxycodone/saline self-administration period (by which time, the adolescent group had reached young adulthood; postnatal day 71) (Adriani and Laviola, 2003), and after the period when classic MOP-r agonist withdrawal or tolerance effects are usually studied (Zhou et al, 2006; Kumar et al, 2008; Seip et al, 2012; Seip-Cammack et al, 2013). Overall, adolescent and adult oxycodone self-administration led to differential adaptations of oxycodone-induced CPP, locomotor activity, and antinociceptive effects, when measured in young adulthood.…”

Expression of brain-derived neurotrophic factors, neurotrophin-3, and neurotrophin-4 in the nucleus accumbens during heroin dependency and withdrawal

“…On day 9, the dose was 27 mg/kg. This pattern of heroin administration has been shown to induce physiological dependence in rats 21. Rats in the control group were administered saline treatment with the same procedure.…”

Effects of post-training heroin and d-amphetamine on consolidation of win-stay learning and fear conditioning

“…The highest heroin dose (i.e. 3 mg/kg) was not included because, in heroin-naïve rats, it produced behavioral stupor (Seip et al, 2012) and even mortality due to depression of respiratory functions (two rats were lost in Experiments 1A and 2). Third, 24 additional rats were assigned to one of three groups receiving post-training injections of vehicle (V Del), 0.03 mg/ kg heroin (0.03H Del) or 0.5 mg/kg d-amphetamine (0.5A Del), delayed by 4 h after termination of testing.…”