Protein preference and elevated plasma FGF21 induced by dietary protein restriction is similar in both male and female mice.

Animals that are moderately protein restricted respond to this dietary stress by increasing consumption of protein-containing foods. This is true in many species, including rodents. Rodent models of protein restriction have typically relied on only male subjects, and there are plausible reasons why female rodents may respond differently to dietary protein restriction. To address this gap in knowledge, the current experiments examined protein preference after two weeks on a 5% protein diet or 20% protein control diet, in male and female mice. We found that female protein-restricted mice, like male protein-restricted mice, increase consumption of 4% casein (protein) relative to 4% maltodextrin (carbohydrate) when presented with both simultaneously. Interestingly, this increased consumption was due to more bursts in females and more licks per burst in males, indicating possible differences in mechanism by which increased intake is achieved. Stage of the estrous cycle did not affect female responses. Moreover, we measured plasma fibroblast growth factor 21 (FGF21) - a hormone induced by protein restriction and necessary for protein preference - in male and female mice. Here, we found no statistical differences between protein-restricted males, females in diestrus, or females in proestrus. In non-restricted mice FGF21 levels were low, but significantly higher in females in proestrus than females in diestrus or males. Overall, these experiments highlight the importance of including female subjects in studies of food choice and macronutrient restriction.

Sampling phasic dopamine signaling with fast-scan cyclic voltammetry in awake, behaving rats.

Fast-scan cyclic voltammetry (FSCV) is an electrochemical technique that permits the in vivo measurement of extracellular fluctuations in multiple chemical species. The technique is frequently utilized to sample sub-second (phasic) concentration changes of the neurotransmitter dopamine in awake and behaving rats. Phasic dopamine signaling is implicated in reinforcement, goal-directed behavior, and locomotion, and FSCV has been used to investigate how rapid changes in striatal dopamine concentration contribute to these and other behaviors. This unit describes the instrumentation and construction, implantation, and use of components required to sample and analyze dopamine concentration changes in awake rats with FSCV.

Heterogeneity of dopamine neuron activity across traits and states.

Midbrain dopamine neurons fire irregularly, with interspersed clusters of high-frequency spikes, commonly called 'bursts'. In this review we examine such heterogeneity in activity, and provide insight into how it can participate in psychiatric conditions such as drug addiction. We first describe several techniques used to evaluate dopamine neuron activity, and comment on the different measures that each provides. We next describe the activity of dopamine neurons in 'basal' conditions. Specifically, we discuss how the use of anesthesia and reduced preparations may alter aspects of dopamine cell activity, and how there is heterogeneity across species and regions. We also describe how dopamine cell firing changes throughout the peri-adolescent period and how dopamine neuron activity differs across the population. In the final section, we discuss how dopamine neuron activity changes in response to life events. First, we focus attention on drugs of abuse. Drugs themselves change firing activity through a variety of mechanisms, with effects on firing while drug is present differing from those seen after drug discontinuation. We then review how stimuli that are rewarding, aversive, or salient can evoke changes in firing rate and discharge pattern of dopamine neurons, and provide behavioral relevance of dopamine signaling. Finally, we discuss how stress can modulate dopamine neuron firing and how this may contribute to the role that stressful experiences play in psychiatric disorders such as addiction and depression.

Genetic background influences the behavioural and molecular consequences of neurokinin-1 receptor knockout.

Genetic background affects animal phenotype and therefore is of particular relevance to studies using genetically manipulated mice. Strain differences in hypothalamic-pituitary-adrenocortical (HPA) axis activity may contribute to background-specificity of some mutations. Here, we analysed components of the HPA axis in mice lacking a functional neurokinin-1 receptor (NK1-/-) on two backgrounds: backcrossed C57BL/6 (B6) and mixed C57BL/6 x 129/sv (129B6). We hypothesized that HPA axis activity would vary between these strains, leading to differences in the NK1-/- phenotype. We compared levels of plasma corticosterone between the groups, and found 129B6 mice exhibited elevated levels of stress-induced corticosterone compared with B6 mice, regardless of genotype. Although the level of basal corticotrophin-releasing factor and stress-induced c-fos mRNAs did not differ between the genotypes of either strain, examination of glucocorticoid receptor immunoreactivity within the hippocampus revealed that NK1-/- mice on the 129B6 background had elevated expression compared with wild-type, whilst there was no difference between genotypes in the B6 strain. Similarly, hippocampal neurogenesis in NK1-/- mice was greater than in wild-type on the 129B6 strain, and did not differ between genotypes on the B6 background. Finally, novelty- and morphine-induced locomotion were assessed. NK1-/- mice on the 129B6 background exhibited hyperlocomotion in response to novelty and greater sensitivity to the locomotor-stimulating properties of morphine than wild-type. In contrast, in B6 mice, no differences were observed between genotypes for either locomotor behaviour. In summary, we find that HPA axis activity differs between the strains and that there are profoundly background-specific effects of the NK1 receptor mutation.