Long-Term Effects of Adverse Maternal Care on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function of Juvenile and Adolescent Macaques.

Early life adversity (ELA) is a known risk factor for psychopathology, including stress-related anxiety and depressive disorders. The underlying mechanisms and developmental changes remain poorly understood. A likely underpinning is the impact of ELA on the development of stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis.

Regulator of G protein signalling 14 (RGS14) protein expression profile in the adult mouse brain.

Regulator of G protein signalling 14 (RGS14) is a multifunctional signalling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with monkey brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra and amygdala.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits.

Regulator of G Protein Signaling 14 protein expression profile in the adult mouse brain.

Regulator of G protein signaling 14 (RGS14) is a multifunctional signaling protein that serves as a natural suppressor of synaptic plasticity in the mouse brain. Our previous studies showed that RGS14 is highly expressed in postsynaptic dendrites and spines of pyramidal neurons in hippocampal area CA2 of the developing mouse brain. However, our more recent work with adult rhesus macaque brain shows that RGS14 is found in multiple neuron populations throughout hippocampal area CA1 and CA2, caudate nucleus, putamen, globus pallidus, substantia nigra, and amygdala in the adult rhesus monkey brain.

RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease.

RGS14 is a multifunctional scaffolding protein that is highly expressed within postsynaptic spines of pyramidal neurons in hippocampal area CA2. Known roles of RGS14 in CA2 include regulating G protein, H-Ras/ERK, and calcium signaling pathways to serve as a natural suppressor of synaptic plasticity and postsynaptic signaling. RGS14 also shows marked postsynaptic expression in major structures of the limbic system and basal ganglia, including the amygdala and both the ventral and dorsal subdivisions of the striatum.

RGS14 Regulation of Post-Synaptic Signaling and Spine Plasticity in Brain.

The regulator of G-protein signaling 14 (RGS14) is a multifunctional signaling protein that regulates post synaptic plasticity in neurons. RGS14 is expressed in the brain regions essential for learning, memory, emotion, and stimulus-induced behaviors, including the basal ganglia, limbic system, and cortex. Behaviorally, RGS14 regulates spatial and object memory, female-specific responses to cued fear conditioning, and environmental- and psychostimulant-induced locomotion.

RGS14 modulates locomotor behavior and ERK signaling induced by environmental novelty and cocaine within discrete limbic structures.

Rationale: In rodents, exposure to novel environments or psychostimulants promotes locomotion. Indeed, locomotor reactivity to novelty strongly predicts behavioral responses to psychostimulants in animal models of addiction. RGS14 is a plasticity-restricting protein with unique functional domains that enable it to suppress ERK-dependent signaling as well as regulate G protein activity.

Effects of early life stress on cocaine self-administration in post-pubertal male and female rhesus macaques.

Rationale: Early life stress (ELS), including childhood maltreatment, is a predictive factor for the emergence of cocaine use disorders (CUDs) in adolescence.

Objective: Accordingly, we examined whether post-pubertal male and female rhesus macaques that experienced infant maltreatment (maltreated, n = 7) showed greater vulnerability to cocaine self-administration in comparison with controls (controls, n = 7).

Methods: Infant emotional reactivity was measured to assess differences in behavioral distress between maltreated and control animals as a result of early life caregiving.

A review of nonhuman primate models of early life stress and adolescent drug abuse.

Adolescence represents a developmental stage in which initiation of drug use typically occurs and is marked by dynamic neurobiological changes. These changes present a sensitive window during which perturbations to normative development lead to alterations in brain circuits critical for stress and emotional regulation as well as reward processing, potentially resulting in an increased susceptibility to psychopathologies. The occurrence of early life stress (ELS) is related to a greater risk for the development of substance use disorders (SUD) during adolescence.