Isolation-reared macaques are hyposensitive to stimuli in a two-bottle choice paradigm

Diminished pleasure in activities (anhedonia) is a central symptom of major depression. Willner et al (1991) reported a rodent model of anhedonia after chronic mild stress (CMS) exposure defined as reduced preference for sweetened water (vs. unsweetened) in a 2-bottle choice procedure. This was reversed by chronic antidepressants. Isolation-reared rhesus macaques also have behavioral abnormalities that can be reversed by antidepressants. We hypothesized that, like CMS rats, their preference for sweetened water would be reduced in a 2-bottle choice procedure (water+sucrose at 7 concentrations vs water). We also measured intake of bitter solutions (quinine+water at 4 concentrations vs water), to test for a more general diminished responsiveness to stimuli. Isolation-reared macaques (3 female, 1 male) and controls (5 female) matched for age and body weight (5-8 kg, 4-5 y.o.) were individually housed with a 23 hr/day water restriction schedule. Animals had access to tap water in 2 identical bottles for 1 hr/day. After acclimation to the restriction schedule and between experiments, baseline water consumption was monitored daily. All procedures were monitored by the IACUC. Animals were healthy throughout the study. In the 1st experiment, 1 bottle contained 1 of 7 sucrose concentrations (2.74-175. mM), randomly presented. The bottles were refilled 30 min. after the start of the access period. The 2nd experiment was similar to the 1st, except that 1 of 4 quinine-HCl concentrations (0.1-3.0 mM) was presented for 4 days as described for sucrose. Bottle positions were alternated daily to control for position preference. Fluid consumption was measured at the middle and end of access. Because baseline fluid consumption correlated with body weight, data were analyzed as ml/kg. All animals consumed more sweetened water than tap water when available, but the difference between sweetened and tap water consumption was less for isolates than for controls. Isolation-reared macaques consumed less sweetened water than controls (75-80%) and consumed more quinine-flavored water (0.1-3.0 mM) than controls. Isolate consumption of tap water during sucrose presentation was greater than controls (114-157%). Baseline fluid consumption did not differ between groups. The data on sweetened water consumption suggest that the isolation-reared macaque is a valid animal model of depression. When consumption of both sweet and bitter solutions are considered, the data suggest that the observed “anhedonia” in this procedure is mediated by a reduction in intensity of both appetitive and aversive properties of stimuli, rather than a selective increase in either the appetitive or aversive properties. This procedure yields a simple index of sensitivity to stimuli in a non-human primate model of depression.