Complex motivated behaviors for natural rewards following a binge-like regimen of morphine administration: mixed phenotypes of anhedonia and craving after short-term withdrawal

Abstract

The anhedonia-like behaviors following about 1-week withdrawal from morphine were examined in the present study. Male rats were pretreated with either a binge-like morphine paradigm or daily saline injection for 5 days. Three types of natural reward were used, food reward (2.5, 4, 15, 30, 40, and 60% sucrose solutions), social reward (male rat) and sexual reward (estrous female rat). For each type of natural stimulus, consummatory behavior and motivational behaviors under varied testing conditions were investigated. The results showed that the morphine-treated rats significantly reduced their consumption of 2.5% sucrose solution during the 1-h consumption testing and their operant responding for 15, 30, and 40% sucrose solutions under a fixed ratio 1 (FR1) schedule. However, performance under a progressive ratio (PR) schedule increased in morphine-treated rats reinforced with 60% sucrose solution, but not in those reinforced with sucrose concentrations lower than 60%. Pretreatment with morphine significantly decreased the male rats' ejaculation frequency (EF) during the 1-h copulation testing, and impaired the maintenance of appetitive motivations to sexual and social stimuli under a free-approach condition. Moreover, the morphine-treated rats demonstrated a diminished motivation to approach social stimulus in the effort-based appetitive behavior test but showed a remarkable increase in motivation to approach sexual stimulus in the risky appetitive behavior test. These results demonstrated some complex motivated behaviors following about 1 week of morphine withdrawal: (1) The anhedonia-like behavior was consistently found in animals withdrawn from morphine. However, for a given reward, there was often a dissociation of the consummatory behaviors from the motivational behaviors, and whether the consummatory or the motivational anhedonia-like behaviors could be discovered heavily depended on the type and magnitude of the reward and the type of testing task; (2) These anhedonia-like behaviors coexisted with a craving for the high-incentive reward which was evidenced by the increased PR performance for the 60% sucrose solution and the heightened risky appetitive behavior for the sexual stimulus. The craving for the high-incentive reward alongside with the impaired inhibitory control in drug-withdrawn subjects might form one of psychological mechanisms underlying drug relapse after withdrawal.

Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine

“…Anhedonia, a core symptom of depression and other neuropsychiatric disorders (APA, 2015), encompasses not only the loss of the capacity to experience pleasure, but also deficits in other discrete reward-related processes interpreted as a loss of interest including reward evaluation, and blunted cost-benefit analysis as well as the loss of the ability to initiate and maintain effort-related behaviors (Der-Avakian & Markou, 2012). Similarly, impaired motivated behaviors directed towards natural rewards following drug withdrawal can take on a complex and multifaceted aspect (Bai, Li, Lv, Liu, & Zheng, 2014). One of our previous studies suggests that the anhedonia-like behaviors, as identified as deficits to engage with natural rewards (sucrose, social and sexual rewards) can be revealed, only after short-term morphine withdrawal, when more than one reward magnitude or appetitive behavioral measure is used (Bai, et al, 2014).…”

“…Similarly, impaired motivated behaviors directed towards natural rewards following drug withdrawal can take on a complex and multifaceted aspect (Bai, Li, Lv, Liu, & Zheng, 2014). One of our previous studies suggests that the anhedonia-like behaviors, as identified as deficits to engage with natural rewards (sucrose, social and sexual rewards) can be revealed, only after short-term morphine withdrawal, when more than one reward magnitude or appetitive behavioral measure is used (Bai, et al, 2014).…”

“…Thus, while both preclinical and clinical studies have documented that sensitivity to stress is increased in drug dependent individuals over the course of protracted abstinence (Heilig, et al, 2010), the nature of the interaction between stress and withdrawal-induced motivational deficits after protracted abstinence from opiates remain poorly understood. Thus we investigated the influence of acute stress over motivational deficits in rats withdrawn from a binge-like morphine treatment paradigm, previously shown both to result in dependence persisting for a long time after the cessation of drug exposure (Nestler & Aghajanian, 1997), and to induce anhedonic behaviors after short-term withdrawal (Bai, et al, 2014).…”

“…For this, we measured, after protracted withdrawal, the influence of acute, shock-induced, stress, on the propensity of male Sprague Dawley rats to approach, and interact with, two natural rewards (social and sexual) of different incentive value, in three appetitive behavioral tasks with increasing cost/benefit ratio: simple, effort-based and conflict-based tests (Bai, et al, 2014).…”

Differential effects of opioid receptor modulators on motivational and stress-coping behaviors in the back-translational rat IFN-α depression model

“…The effects of morphine and U50 488 were only observed at the 30min test timepoint, at later time-points the effect disappeared. MORs have a complex relationship with hedonic and appetitive behaviors: for example, Zhang and colleagues demonstrated morphine withdrawal resulted in decreased motivation to obtain a natural reinforcement [44], while others showed morphine withdrawal increased operant responding for sucrose reward, but only for a 60% or greater sucrose solution [45]. These data suggest that morphine dosing, time of withdrawal and concentration of sucrose can easily alter results obtained.…”