Chronic stress deficits in reward behaviour co-occur with low nucleus accumbens dopamine activity during reward anticipation specifically.

Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology.

Engagement of basal amygdala-nucleus accumbens glutamate neurons in the processing of rewarding or aversive social stimuli.

Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to estrous female (social reward, SR) and/or aggressive-dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c-Fos expression in a high and similar number/density of BA-NAc neurons in the anteroposterior intermediate BA (int-BA), whereas activation was predominantly by SA in posterior (post-)BA. In Fos-TRAP2 mice, compared with SR-SR or SA-SA controls, exposure to successive presentation of SR-SA or SA-SR, followed by assessment of tdTomato reporter and/or c-Fos expression, demonstrated that many int-BA-NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int-BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int-BA-NAc neurons during social and sexual interactions. Therefore, populations of BA-NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence-specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio-emotional processing.

The Anticonvulsant Lamotrigine Reduces Bout-Like Alcohol Drinking in Rats.

We used an optical lickometer system to study drinking microstructure and effect of lamotrigine in voluntary alcohol-drinking rats. We showed that, similar to humans, animals differ by their drinking microstructure where some consume alcohol exclusively in a bout-like patterns. The study suggests that anticonvulsants, such as lamotrigine, may be one treatment strategy specifically affecting this type of drinking.

Modulation of responses to visual stimulus onset and offset by chronic alcohol consumption and withdrawal in the rat visual cortex and lateral geniculate nucleus.

In the visual system, chronic alcohol consumption and subsequent abstinence strongly modulate processing of sensory information, which could interfere with the actions in our daily lives. Although previous studies showed histological and electrophysiological changes in the retina and visual cortex during chronic alcohol consumption and abstinence, there is still a lack of information related to the effect of alcohol on: 1) different stages of visual information processing; and 2) responses of stimulus onset (ON) and offset (OFF). In order to answer these questions, we recorded visual evoked potentials (VEPs), elicited by onset and offset of a 500-ms stimulus, following long-term alcohol consumption (8 weeks) and abstinence (3 weeks) in freely moving Wistar rats. Latency and amplitude of five components in the visual cortex (N1VC, P2VC, N2VC, P3VC, N3VC) and three components in the lateral geniculate nucleus (P1LGN, N1LGN, P2LGN) were analyzed. The results showed that long-term chronic alcohol consumption and abstinence have a strong long-term and, in some cases, irreversible impact on visual information processing. Both of these conditions modulate only the last stage of stimulus onset processing at the level of the visual cortex, but not at the level of the lateral geniculate body. Response to the stimulus offset is more susceptible to the effect of alcohol consumption and/or abstinence and is modulated at both the visual cortex and lateral geniculate nucleus levels. This modulation at different stages of the information processing chain can result in inaccurate processing of visual stimuli parameters and can lead to changes in perception of stimulus duration and intensity.

Effect of ethanol on the visual-evoked potential in rat: dynamics of ON and OFF responses.

The effect of acute ethanol administration on the flash visual-evoked potential (VEP) was investigated in numerous studies. However, it is still unclear which brain structures are responsible for the differences observed in stimulus onset (ON) and offset (OFF) responses and how these responses are modulated by ethanol. The aim of our study was to investigate the pattern of ON and OFF responses in the visual system, measured as amplitude and latency of each VEP component following acute administration of ethanol. VEPs were recorded at the onset and offset of a 500 ms visual stimulus in anesthetized male Wistar rats. The effect of alcohol on VEP latency and amplitude was measured for one hour after injection of 2 g/kg ethanol dose. Three VEP components - N63, P89 and N143 - were analyzed. Our results showed that, except for component N143, ethanol increased the latency of both ON and OFF responses in a similar manner. The latency of N143 during OFF response was not affected by ethanol but its amplitude was reduced. Our study demonstrated that the activation of the visual system during the ON response to a 500 ms visual stimulus is qualitatively different from that during the OFF response. Ethanol interfered with processing of the stimulus duration at the level of the visual cortex and reduced the activation of cortical regions.