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1

Role of alpha2-adrenergic receptors in ventral tegmental area in the phasic dopamine release into basolateral amygdala in stressed and non stressed rats

100%
Bernacka J., Kielbinska M., Solecki W. B.
Acta Neurobiologiae Experimentalis
|
2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: In the ventral tegmental area (VTA), norepinephrine (NA) promotes phasic dopamine (DA) release in the forebrain, thus regulating conditioned behaviors, such as fear conditioning. We recently demonstrated that α2-AR blockade in the VTA reduces DA release in the mesolimbic but not mesocortical pathway. Under the influence of stress, downregulation of α2-AR occurs in stria terminalis, therefore we hypothesize that the mechanism in VTA is similar. The net effect of α2-AR signaling on DA release may depend on the plasticity related to factors such as acute stress. AIM(S): The aim of this study is to demonstrate the impact of acute stress on the ability of α2-AR signalling in stressed versus naïve, non-stressed, rats to modulate phasic DA release in the basolateral amygdala (BLA). METHOD(S): For the study of dopaminergic signaling, fast-scan cyclic voltammetry was used in urethane anesthetized rats. The stimulation electrode, together with the guide cannula, was placed in the VTA, while the recording carbon‑fiber microelectode in BLA. In the case of stressed rats, animals were subjected to fear conditioning (0.9‑mA electric footshock) 24 hours before FSCV. RESULTS: Intra‑VTA administration of the α2-AR selective antagonist RX‑821002 strongly reduced phasic DA release in the BLA in naïve rats. In contrast, only modest attenuation of DA by RX‑821002 was observed in the BLA of stressed animals. CONCLUSIONS: Our results are consistent with the idea that α2-AR signalling in various structures undergoing NAergic modulation is subject to plasticity related to stress. Here, we show that an acute stressful stimulus is sufficient to elicit this form of plasticity, potentially via α2‑AR downregulation.
2

Intra ventral tegmental area noradrenergic receptor signalling regulates CUE-induced fear memory retrieval

88%
Zajda K., Drwiega G., Wira P., Szklarczyk K., Solecki W. B.
Acta Neurobiologiae Experimentalis
|
2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: Noradrenergic receptors (α‑AR) in the ventral tegmental area (VTA) regulate phasic dopamine release in the mesolimbic, but not in the mesocortical pathway. Accordingly, the α‑ARs modulate conditioned behaviours, such as acquisition of fear memories. Importantly, the role of the VTA noradrenergic signaling in fear memory retrieval remain unclear. AIM(S): The aim of the study was to investigate the role of α1‑AR and α2-AR in VTA in the retrieval of conditioned stimulus (CS)‑induced fear memories. In control studies, we investigate their role in the locomotor activity and anxiety‑like behaviour. METHOD(S): We performed fear conditioning and open field tests in adult male, Spraque‑Dawley rats combined with intra‑VTA microinfusions. The fear conditioning consisted of two phases: training during which CS was associated with footshock, and retrieval of the conditioned fear memory. Retrieval test was preceded by intra‑VTA administration of α1‑AR and α2-AR antagonist (terazosin 1 µg/side and RX 821002 2.7 µg/side) and conducted in a novel context in which presentation of CS induced fear responses. RESULTS: We demonstrated that α1-AR blockade in the VTA decreased freezing responses during retrieval of CS‑induced fear memory. In contrast, α2AR blockade had no effects. Furthermore, neither blockade of α1-AR and α2-AR had no effects on locomotor activity and anxiety‑like behavior. CONCLUSIONS: Here, we demonstrated a potential role of the VTA noradrenergic signaling in fear memory retrieval. These results indicate that the noradrenergic signalling in the VTA modulates CS-fear induced responses predominantly via α1‑AR.
3

Characteristics of rat ventral tegmental area GABAergic-like neuronal responses to an aversive stimulus

76%
Drwiega G., Walczak M., Pradel K., Izowit G., Solecki W. B., Blasiak T.
Acta Neurobiologiae Experimentalis
|
2019
|
tom 79
|
nr Suppl.1
INTRODUCTION: The ventral tegmental area (VTA) is a major source of dopamine in the mammalian brain. Previous studies have confirmed that the pattern of VTA dopamine (DA) cell spontaneous activity is tonic rather than phasic during an activation state in contrast to deactivation (SWA), generated by urethane anesthesia. However, little is known about the second largest neuronal population in the VTA – GABA-ergic cells, which best known functional role is to inhibit the surrounding DA neurons, for e.g., in response to an aversive stimulus. AIM(S): The aim of our study was to investigate how VTA non-DA neurons respond to an aversive stimulus (footshock) and whether this reaction changes with an alterations in the brain states elicited by urethane anesthesia application. METHOD(S): We performed extracellular in vivo recordings of non-DA neurons combined with simultaneous recording of local field potentials from the hippocampus. Recordings were performed using SD‑TH‑Cre+/‑ rats under urethane anesthesia and electric footshocks were applied (45 per state) to the hindpaw of the animal in both brain states. We used optogenetics to identify the phenotype (DA vs. non-DA cell phenotype) of the footshock responsive cells by photo‑tagging. RESULTS: GABAergic-like (non-DA) cells respond to the footshock with either excitation (36%) or inhibition (16%) of their activity regardless of the brain states. Interestingly, a fraction of those non‑DA cells (20%) reacted with inhibition during activation and excitation during a deactivation state. The rest of the cells react with no‑responses in at least one state (28%). CONCLUSIONS: In line with previous studies, we observed a population of non-DA cells that react with excitation in response to footshocks. Interestingly, we also observed non-DA cells that were inhibited and populations that reacts depending on current brain state. Our results indicate a more complex role of GABAergic cells in response to footshock than previously assumed.
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