Effect of Acute Stress on the Expression of BDNF, trkB, and PSA-NCAM in the Hippocampus of the Roman Rats: A Genetic Model of Vulnerability/Resistance to Stress-Induced Depression

The Roman High-Avoidance (RHA) and the Roman Low-Avoidance (RLA) rats, represent two psychogenetically-selected lines that are, respectively, resistant and prone to displaying depression-like behavior, induced by stressors. In the view of the key role played by the neurotrophic factors and neuronal plasticity, in the pathophysiology of depression, we aimed at assessing the effects of acute stress, i.e., forced swimming (FS), on the expression of brain-derived neurotrophic factor (BDNF), its trkB receptor, and the Polysialilated-Neural Cell Adhesion Molecule (PSA-NCAM), in the dorsal (dHC) and ventral (vHC) hippocampus of the RHA and the RLA rats, by means of western blot and immunohistochemical assays. A 15 min session of FS elicited different changes in the expression of BDNF in the dHC and the vHC. In RLA rats, an increment in the CA2 and CA3 subfields of the dHC, and a decrease in the CA1 and CA3 subfields and the dentate gyrus (DG) of the vHC, was observed. On the other hand, in the RHA rats, no significant changes in the BDNF levels was seen in the dHC and there was a decrease in the CA1, CA3, and DG of the vHC. Line-related changes were also observed in the expression of trkB and PSA-NCAM. The results are consistent with the hypothesis that the differences in the BDNF/trkB signaling and neuroplastic mechanisms are involved in the susceptibility of RLA rats and resistance of RHA rats to stress-induced depression.

Partial Reinforcement Reduces Vulnerability to Anti-anxiety Self-medication During Appetitive Extinction

Inbred rats from the Roman low-avoidance strain (RLA-I), but not from the Roman high-avoidance strain (RHA-I) increased preference for ethanol after being exposed to sessions of appetitive extinction (Manzo et al. Physiol Behav 2014 123:86-92). RLA-I rats have shown greater sensitivity than RHA-I rats to a variety of anxiogenic situations, including those involving reward loss. Such increased fluid preference did not occur after acquisition (reinforced) sessions or in control groups with postsession access to water, rather than ethanol. Because ethanol has anxiolytic properties in tasks involving reward loss, oral consumption after extinction sessions was interpreted as anti-anxiety or emotional self-medication (ESM). The present research was an attempt to reduce or eliminate the ESM effect in RLA-I rats by giving them 50% partial reinforcement training during the acquisition of an instrumental response, a treatment known to induce resilience to loss-induced anxiety. As expected, partially reinforced RLA-I rats showed a higher resistance to extinction in comparison to continuously reinforced animals, displaying lower ethanol consumption than continuously reinforced rats during the postsession preference test. Partial and continuous control groups receiving water during the preference tests showed no changes in preference. These results suggest that exposure to reward uncertainty typical of partial reinforcement training can reduce ESM in rats genetically selected for high levels of anxiety.

Incentive Relativity: Gene-Environment Interactions

Reward loss experiences are among the main sources of emotional stress that humans face throughout their lives. In the animal laboratory, it has been repeatedly shown that the unexpected omission or devaluation of a reinforcer triggers a physiological, cognitive, and behavioral state called frustration. This state involves emotional mechanisms that resemble those unleashed by the presentation of other aversive stimuli, inducing similar stress responses through the activation of brain circuits involved in fear and anxiety. Although this hypothesis has been supported by behavioral, pharmacological, hormonal, and neurobiological evidence, only a few studies have focused on the neurogenetic basis of frustration in animals. This review focuses on the gene-environment interactions that determine the emotional response under conditions of reward loss. Behavioral and genetic correlates of frustration are reviewed in two strains of animals selected on the basis of extreme differences in active avoidance learning: inbred Roman High- (RHA-I) and Roman Low-Avoidance (RLA-I) rats. The review shows the usefulness of Roman strains for neurogenetic research and sets out unsolved questions regarding gene-environment interactions underlying behavior induced by incentive loss.