Intake of and preference for sweet solutions are attenuated in morphine-withdrawn rats.

Abstract

The hypothesis that intake of sweet solutions is partially controlled by endogenous opioid peptides was tested in 2 experiments that examined the effects of repetitive morphine administration and withdrawal on subsequent intake of and preference for saccharin solutions in rats. Experiment 1 established that 17 hr after morphine withdrawal, rats consumed less saccharin, but not less water, than did controls. The groups did not differ 8 days later. In Experiment 2, using a 2-bottle saccharin-preference test, rats exhibited a reduced preference to saccharin solutions (1, 3, 9, 30, or 60 mM) for 6 days after morphine withdrawal. The difference between the groups was most pronounced at the most preferred concentrations (9 and 30 mM). The results suggest that cross-tolerance occurs between morphine and the opioid-mediated hedonic effects of sweet solutions.

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

“…Accordingly, the decreased consumption of 2.5 and 4% sucrose solutions may suggest a consummatory anhedonia for the sweet solution in animals withdrawn from morphine. Our findings corroborate previous reports (Lieblich et al, 1991; Hellemans et al, 2002) that opiate-withdrawn rats consume less of a sweet solution than do drug-naïve control subjects. However, in the present study, the manifestation of this consummatory anhedonia-like behavior critically depended on reward magnitude of the solutions (i.e., the sweetness of the sucrose solution), reflecting a deficit in the hedonic response only to the small reward and thus a probable reduction in appetite for such reward.…”

“…As is stated in the introduction, there exist large inconsistencies in the present preclinical literatures, i.e., the decreases (anhedonia-like), the increases (sensitization) or no change in hedonic response/motivation to natural stimuli following drug withdrawal (Lieblich et al, 1991; Barr et al, 1999; Barr and Phillips, 1999; Fiorino and Phillips, 1999; Hellemans et al, 2002; Russig et al, 2003; Cui et al, 2004; Nocjar and Panksepp, 2007; Zhang et al, 2007; Der-Avakian and Markou, 2010; Galaj et al, 2013). This is not surprising since the dosage/duration of drug pretreatment, withdrawal period, the type and magnitude of the supposed rewarding stimulus (e.g., the sweet pellet/liquid with different concentrations, sexual stimulus, or social stimulus), and the way and/or the amount of difficulty to get them may all play significant roles in the behavioral outputs.…”

“…Usually, only one type of the natural reward such as food or sexual reward was adopted in the majority of preclinical literatures. For example, the consumptive behaviors for sucrose/sweet pellet and operant responding on a FR or PR schedule of reinforcement have been evaluated as behavioral measures of anhedonia (Lieblich et al, 1991; Barr and Phillips, 1999; Hellemans et al, 2002; Russig et al, 2003; Lesage et al, 2006; Zhang et al, 2007; Cooper et al, 2010; Der-Avakian and Markou, 2010; Galaj et al, 2013). In the experiments performed with social and/or sexual rewards, the effects of drug withdrawal on copulatory behavior or appetitive motivation for the rewarding stimulus (free approach or conditioned approach) have been assessed (Ferrari and Giuliani, 1997; Barr et al, 1999; Fiorino and Phillips, 1999; Nocjar and Panksepp, 2002, 2007; Cui et al, 2004).…”

Extended Heroin Access Increases Heroin Choices Over a Potent Nondrug Alternative

“…Extended heroin access and HW were associated with a robust escalation of heroin intake, as previously shown (Deneau et al, 1969;Ahmed et al, 2000;Chen et al, 2006;Vendruscolo et al, 2011), and with the emergence of clear motivational markers of dependence , such as a blockade of normal body weight growth and a suppression of saccharin responding and intake. The latter phenomenon increased with past heroin consumption but gradually returned to normal after prolonged abstinence, confirming previous research in rats (Parker et al, 1973;Lieblich et al, 1991). In theory, HW could have contributed to increased heroin choices after extended heroin access by either increasing the reinforcing value of heroin or, alternatively, by decreasing the value of sweet water, or by producing both effects (Ahmed et al, 2000;Koob and Le Moal, 2001).…”

The relationship between opioid and sugar intake: Review of evidence and clinical applications

“…Heroin addicts who initiated methadone maintenance treatment typically demonstrated significant weight gain, possibly related to their expressed strong cravings for sweets during protracted abstinence (25). The rats in acute opiate withdrawal also express a similar increased craving for sweets (26). A study of autopsies of Swedish IV drug users recorded between 1988–2000 demonstrates that while 36% of heroin users were overweight (BMI>25), 43.1% of methadone users were overweight (27).…”