An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress

Abstract

Chronic exposure to very mild unpredictable stress has previously been found to depress the consumption of, and preference for, highly palatable sweet solutions. The present study used the place conditioning procedure to investigate whether these effects result from a decreased sensitivity to reward. Rats were subjected to chronic mild unpredictable stress for a total of 4 weeks. During weeks 3 and 4, they received four training trials, in which rewards were presented in a distinctive environment, and four further non-rewarded trials in a different environment. The rewards used in different experiments were food pellets, dilute (0.7%) and concentrated (34%) sucrose solutions, and dl-amphetamine sulphate (0.5 and 1.0 mg/kg). In all experiments, non-stressed animals showed an increase in preference for the environment associated with reward; in stressed animals, these effects were abolished or greatly attenuated. Chronic unpredictable mild stress, which may be comparable in intensity to the difficulties people encounter in their daily lives, appears to cause a generalized decrease in sensitivity to rewards.

Food Intake and Reward Mechanisms in Patients with Schizophrenia: Implications for Metabolic Disturbances and Treatment with Second-Generation Antipsychotic Agents

“…Eating and reward in schizophrenia I Elman et al obesity in schizophrenic patients has been undermined, though, by (1) the lack of consistent hypercortisolemia in nonacutely ill schizophrenia samples (Gispen-de Wied, 2000), (2) the lack of visceral fat accumulation and obesity in drug-naive schizophrenia samples from non-Westernized populations , and (3) weight gain (Thierry et al, 1976;Imperato et al, 1989) K Reinstatement of drug seeking (Shaham et al, 2002) K Self-administration of electric shock (Barrett and Spealman, 1978) K Stress-induced place preference (Bozarth, 1987) m Activity in the NAc and other mesolimbic reward pathways (Phillips et al, 1998;Becerra et al, 2001) K Leads to drug abuse and relapse (Sinha, 2001) K Seeking of mild-to-moderate stress (ie, roller coaster, automobile racing, skydiving, horror movies, etc) perceived as pleasant (Selye, 1976;Goeders, 2002) Drugs mDopaminergic transmission in the NAc and other mesolimbic reward pathways (Hernandez and Hoebel, 1988) Reinstatement of drug seeking and drug self-administration (Shaham et al, 2002) m Activity in the NAc and other mesolimbic reward pathways (Breiter et al, 1997;Volkow et al, 2002b) Mood elevation (Breiter et al, 1997) Chronic Stress kDopaminergic transmission in the NAc and other mesolimbic reward pathways (Puglisi-Allegra et al, 1991;Imperato et al, 1993) k Motivation towards normally pleasurable stimuli (eg, k sucrose consumption, animal homolog of anhedonia; Willner et al, 1987;Papp et al, 1991) k In reward function (Elman et al, 2005) Emotional numbing and anhedonia (American Psychiatric Association, 2000)…”

“…Acute stress activates dopamine transmission in the reward circuitry through enhancement of extracellular dopamine release and/or potentiation of dopamine receptors' affinity and their activity (Thierry et al, 1976;Imperato et al, 1989). Chronic stress exerts an opposite action by decreasing dopaminergic (Puglisi-Allegra et al, 1991;Imperato et al, 1993) neurotransmission and is accompanied by decreased motivation towards normally pleasurable stimuli (Willner et al, 1987;Papp et al, 1991). Furthermore, stress-related negative affective states drive comfort or palatable food consumption as it can alleviate these states (ie, 'selfmedication') via temporary normalization of reward function (Wang et al, 2001), via inhibition of hypothalamic CRF secretion involved in stress-induced anxiety and depression (Dallman et al, 2003) or via priming effects (Wise, 2004) on the mesocorticolimbic dopaminergic system (Thierry et al, 1976;Imperato et al, 1989).…”

“…Prefrontal cortex (PFC) modulates these effects via reciprocal innervation with the hypothalamic-limbic areas (Berthoud, 2004a) by forming subjective hedonic perceptions and integrating them with metabolic signals and with intrapsychic and environmental contexts (Kringelbach, 2005). For the clarity of presentation, the scheme was rendered out-of-scale and simplified to reduce the numbers of the displayed links and structures to those of direct relevance to the main themes of this review.Eating and reward in schizophrenia I Elman et al K Self-administration of electric shock (Barrett and Spealman, 1978) K Stress-induced place preference (Bozarth, 1987) m Activity in the NAc and other mesolimbic reward pathways (Phillips et al, 1998;Becerra et al, 2001) K Leads to drug abuse and relapse (Sinha, 2001) K Seeking of mild-to-moderate stress (ie, roller coaster, automobile racing, skydiving, horror movies, etc) perceived as pleasant (Selye, 1976;Goeders, 2002) Drugs mDopaminergic transmission in the NAc and other mesolimbic reward pathways (Hernandez and Hoebel, 1988) Reinstatement of drug seeking and drug self-administration (Shaham et al, 2002) m Activity in the NAc and other mesolimbic reward pathways (Breiter et al, 1997;Volkow et al, 2002b) Mood elevation (Breiter et al, 1997) Chronic Stress kDopaminergic transmission in the NAc and other mesolimbic reward pathways (Puglisi-Allegra et al, 1991;Imperato et al, 1993) k Motivation towards normally pleasurable stimuli (eg, k sucrose consumption, animal homolog of anhedonia; Willner et al, 1987;Papp et al, 1991) k In reward function (Elman et al, 2005) Emotional numbing and anhedonia (American Psychiatric Association, 2000)Drugs k Dopaminergic transmission in the NAc and other mesolimbic reward pathways (Solomon and Corbit, 1974;Koob and Le Moal, 2001) k Motivation towards normally pleasurable stimuli (Grigson and Twining, 2002) k Activity in the NAc and other mesolimbic reward pathways Little et al, 1999; MartinSoelch et al, 2001a;…”

Hippocampal Cytogenesis Correlates to Escitalopram-Mediated Recovery in a Chronic Mild Stress Rat Model of Depression

“…Sequential exposure to a variety of mild stressors causes behavioral deficits in different paradigms that measure sensitivity to rewards. Thus, CMS suppresses the consumption of and preference for palatable sweet solutions (Willner et al, 1987), and the rewarding properties of food pellets, sweet solutions and amphetamine, as assessed by the place preference conditioning procedure (Papp et al, 1991). CMS furthermore increases thresholds for ventral tegmental self-stimulation, indicating a decreased responsiveness to rewarding stimuli (Moreau et al, 1995).…”

Selective modifications in the nucleus accumbens of dopamine synaptic transmission in rats exposed to chronic stress

“…Longterm exposure to different unavoidable stress protocols decreases DA output in the nucleus accumbens shell (NAcS) and in the mPFC (Di Chiara and Tanda 1997;Gambarana et al 1999b;Mangiavacchi et al 2001), and it impairs responsiveness to both aversive and pleasurable stimuli (Overmier and Seligman 1967;Papp et al 1991;Moreau et al 1992;Gambarana et al 1995;Ghiglieri et al 1997). The impaired responsiveness to environmental stimuli induced by exposure to chronic stress has been used to model two depressive symptoms, hyporeactivity and anhedonia, or lack of motivation, as stressed rats do not show an avoidance response when exposed to avoidable noxious stimuli ) and they do not acquire an appetitive behavior (Ghiglieri et al 1997) or a palatable food-induced place preference (Papp et al 1991). Moreover, the repeated administration of antidepressants, e.g.…”