Enduring increases in anxiety‐like behavior and rapid nucleus accumbens dopamine signaling in socially isolated rats

Abstract

Social isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety-like behavior, impaired sensorimotor gating and increased self-administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2-type autoreceptor activity in the nucleus accumbens core. Long–Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28–77]. After this initial housing period, rats were assessed on the elevated plus-maze for an anxiety-like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety-like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety-like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH-reared rats that were isolated as adults did not develop the anxiety-like behavior or dopamine changes seen in SI-reared rats. Together, our data suggest that early life stress results in an anxiety-like phenotype, with lasting increases in dopamine terminal function.

Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats

“…We have recently shown that blockade of dopaminergic neurotransmission by systemic administration of α-flupenthixol reduces motivation for social play in a lever pressing task, without altering the performance of social play during reinforced periods (Achterberg et al, 2016), although systemic treatment with higher doses of α-flupenthixol does reduce social play behavior . It has been shown that long periods of social isolation after weaning affect mesolimbic dopaminergic activity (Yorgason et al, 2013(Yorgason et al, , 2016Whitaker et al, 2013). Thus, in line with the view that NAc dopaminergic neurotransmission plays a critical role in incentive motivation (Barbano and Cador, 2007;Kelley, 2004;Salamone and Correa, 2012), we hypothesized that animals highly motivated for social play as a result of longer social isolation before testing would be more sensitive to blockade of NAc dopamine receptors.…”

A Protocol for Conventional Sleep Deprivation Methods in Rats

“…Besides, MP does not restrict animal movement throughout the study [22,23]. Generally, animals' exposure to the restricted space that limits their locomotor activities [24] and isolation, can elevate their plasma corticosterone levels, indicating their behavioral and biochemical vulnerability to both immobilization and isolation effects [25,26]. Modified-MP technique can obviate some of the aforementioned behavioral abnormalities [23].…”

Intergenerational transmission of sociality: the role of parents in shaping social behavior in monogamous and non-monogamous species

“…Perhaps missing, though, is investigation of social stressors as well as a comparison of acute and chronic stress exposure. Responses to social and non-social stressors do vary (Branchi et al, 2013), and social stressors, in particular social isolation housing, have been extensively studied in the prairie vole (Grippo et al, 2007b(Grippo et al, ,c, 2009Pan et al, 2009;Ruscio et al, 2007) as well as the rat (Malkesman et al, 2006;Parker and Morinan, 1986;Weiss et al, 2004;Yorgason et al, 2013). Similarly, HPA function varies between acute and chronic stress exposure (see Lightman, 2008 for review).…”