Evaluation of reward processes in an animal model of depression

Abstract

Rationale Anhedonia is a core symptom of major depression. Deficits in reward function, which underlie anhedonia, can be readily assessed in animals. Therefore, anhedonia may serve as an endophenotype for understanding the neural circuitry and molecular pathways underlying depression.Objective Surprisingly, there is scant knowledge regarding alterations in brain reward function after olfactory bulbectomy (OB), an animal model which results in a behavioural syndrome responsive to chronic antidepressant treatment. Therefore, the present studies aimed to assess reward function after bulbectomy. Materials and methods The present study utilized sucrose preference, cocaine-induced hyperlocomotion and intracranial self-stimulation (ICSS) responding to examine reward processes in the OB model.Results Bulbectomized animals showed a marked preference (>90%) for 0.8% sucrose solution compared with water; similar to the preference exhibited by sham controls. Importantly, there were pronounced deficits in brain reward function, as assessed using ICSS, which lasted 8 days before returning to baseline levels. Furthermore, bulbectomized animals were hyper-responsive to the locomotor stimulating properties of an acute and a repeated cocaine regimen. However, no difference in ICSS facilitation was observed in response to an acute cocaine injection. Conclusions Taken together, these results suggest that bulbectomized rats display alterations in brain reward function, but these changes are not long-lasting and thus, not amenable to investigating the effects of pharmacological interventions. However, given that OB animals are hypersensitive to drugs of abuse, bulbectomy may be an appropriate inducing factor for the development of animal models of co-morbid depression and drug dependence.

A single episode of maternal deprivation impairs the motivation for cocaine in adolescent mice

“…Furthermore, in rats, CMS induces an increased immobility in the FST associated with a decrease in reward sensitivity as measured by increased intracranial self-stimulation threshold, attenuated sucrose consumption, decreased preference for alcohol, impaired sexual behaviour and decreased amphetamine and morphine rewarding effects (Willner 2005). Similarly, olfactory bulbectomy that exhibits a high degree of neurochemical similarity to depression induces a decreased sensitivity to reward as shown by a decreased sexual behaviour (Lumia et al 1992), an increased intracranial self-stimulation threshold (Slattery et al 2007) and a reduced cocaine place preference (Calcagnetti et al 1996).…”

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

“…Conversely, the NMDA antagonist ketamine, which primarily 902 depresses ICSS in the absence of explicit stress, also failed to reverse depression of ICSS induced by socialdefeat stress in mice (Donahue et al, 2014). Other research has shown that repeated stress can enhance amphetamine-induced facilitation of ICSS (Lin et al, 2002), whereas effects of cocaine and THC were not altered by olfactory bulbectomy or repeated stress, respectively (Slattery et al, 2007;Fokos and Panagis, 2010). Together, these results illustrate the potential for differential effects of stress as a modulator of abuserelated drug effects in ICSS procedures, but given the prominent role of stress as a risk factor in drug abuse (Neisewander et al, 2012;Volkow et al, 2012), this is a relatively undeveloped theme of research.…”

“…Brain reward systems, including the mesolimbic DA system, have been implicated in mood disorders (Nestler and Carlezon, 2006;Russo and Nestler, 2013), and ICSS has been used in preclinical studies aimed at identifying determinants of stress-related depression of positively reinforced behavior. Regimens of repeated stress, including chronic, intermittent exposure to stressors like restraint and soiled bedding (Moreau et al, 1992(Moreau et al, , 1994 or social defeat (Donahue et al, 2014), have been reported to depress basal ICSS, and ICSS was also depressed by an olfactory bulbectomy model of depression (Slattery et al, 2007). However, other regimens of chronic stress had no effect on ICSS (Fokos and Panagis, 2010) or produced effects that varied across time or across test subjects (Nielsen et al, 2000;Lin et al, 2002).…”

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

“…The sucrose preference test (Willner, 1997), intra-cranial self-stimulation (Slattery et al, 2007), and operant tests such as sucrose pellet reinforcement on a progressive ratio schedule (Ineichen et al, 2012), are examples of relevant readout tests.…”