Biology subjects

Valyear, M. D.

Publications and source records attributed to Valyear, M. D..

3 recordsLinked to original sources

bioRxiv2023

Dissociating the reinforcing and sensory properties of medial accumbens shell dopamine.

Dopamine regulates the frequency of motor actions, but it is unclear whether it similarly regulates the duration of discrete behaviors. Here, we show that dopamine signaling within the medial accumbens shell reinforces actions while simultaneously constraining their duration. When mice hold down a lever to continuously self-stimulate dopamine axons in the medial accumbens shell, hold-downs are rarely longer than 5 seconds, and higher stimulation frequencies elicit shorter, but more numerous, lever hold-downs. This disengaging property of medial accumbens shell dopamine also applies to consummatory behavior, as mice are quicker to both terminate and reinitiate bouts of licking paired with high frequency dopamine axon stimulation. Dopamine D1 receptors underpin this disengaging property of dopamine signaling, as we demonstrate a D1 agonist shortens both self-stimulation hold-downs and bouts of consummatory behavior. Altogether, we uncover an anatomically defined role of dopamine, which is to disengage its own reinforcing properties through D1 receptor signaling.

neuroscience↗

bioRxiv2020

Sex difference in the modulation of responding to an alcohol-predictive cue by an alcohol-associated context

BackgroundIn male rats, physical contexts that are associated with alcohol can invigorate responding to a discrete, alcohol-predictive conditioned stimulus (CS), and amplify priming-induced reinstatement. Here, we examined these effects as a function of biological sex. MethodsMale and female Long-Evans rats were acclimated to drinking ethanol (EtOH, 15% v/v) in their home cages. Next, they were trained to associate an auditory CS (10 s; white noise; 15 trials per session) with EtOH delivery (0.2 ml per CS; 3.0 ml per session) into a fluid port for oral intake. Training occurred in a distinctive context containing specific visual, olfactory, and tactile stimuli. During alternating sessions rats were exposed to a second context where they did not receive EtOH. At test, CS presentations occurred in both contexts without EtOH delivery. Rats then underwent extinction using repeated unreinforced presentations of the CS in both contexts. An alcohol-primed reinstatement test was then conducted, in which 0.2 ml of EtOH was presented both at the start of the session and during the first CS presentation, after which no EtOH was delivered for the remainder of the session. ResultsAt both test and reinstatement, male rats made significantly more CS port-entries in the context associated with alcohol delivery than in the context in which alcohol was never experienced. Unlike males, female rats made a similar number of CS port-entries at test in both the alcohol context and the neutral context. The reinstatement observed in female rats was not affected by context. ConclusionsThese findings identify novel sex differences in the capacity of an alcohol-associated context to modulate responding to a discrete, alcohol-predictive cue.

neuroscience↗

bioRxiv2018

Divergent mesolimbic dopamine circuits support alcohol-seeking triggered by discrete cues and contexts

Discrete and contextual cues that predict alcohol trigger alcohol-seeking. However, the extent to which context influences alcohol-seeking triggered by discrete cues, and the neural mechanisms underlying these responses, are not well known. We show that, relative to a neutral context, a context associated with alcohol persistently elevated alcohol-seeking triggered by a discrete cue, and supported higher levels of priming-induced reinstatement. Alcohol-seeking triggered by a discrete cue in a neutral context was reduced by designer receptor-mediated inhibition of ventral tegmental area (VTA) dopamine neurons in TH::Cre rats. Inhibiting terminals of VTA dopamine neurons in the nucleus accumbens (NAc) core reduced alcohol-seeking triggered by a discrete cue, irrespective of context, whereas inhibiting VTA dopamine terminals in the NAc shell selectively reduced the elevation of alcohol-seeking triggered by a discrete cue in an alcohol context. This dissociation highlights unique roles for divergent mesolimbic dopamine circuits in alcohol-seeking driven by discrete and contextual environmental cues.

neuroscience↗