Role of ventral tegmental area dopamine neurons in fear memory retention in post-traumatic stress disorder model rats.

Ventral tegmental area (VTA) dopamine (DA) neurons have been found to substantially associate with post-traumatic stress disorder (PTSD) pathology, however, whether and how these DA neurons affect fear memory management in PTSD individuals remains largely unknown. In this study, we utilized auditory conditioned foot-shock to evaluate the fear memory retrieval and retention characteristics in a single prolonged stress-induced PTSD rat model. We employed chemogenetic technology to specifically activate VTA DA neurons to examine the freezing behaviors responding to the conditioned stimuli. In vivo extracellular electrophysiological analyses were used to identify VTA DA neuronal firing alterations due to the chemogenetic activation. The results demonstrated that PTSD model rats showed comparable fear memory retrieval (Day 2 after the conditioned foot-shock), but significant enhancements in fear memory retention (Day 8 after the conditioned foot-shock), compared to normal control rats. Chemogenetic activation of VTA DA neurons markedly diminished the retention of fear memory in PTSD model rats, which appeared concomitantly with increases in the firing activities of the DA neurons. These findings revealed that PTSD induced the persistence of fear memory, which could be attenuated by activation of VTA DA neurons. It is presumed that VTA dopaminergic signals may serve as a prospective option for PTSD treatment.

Activation of ventral tegmental area dopaminergic neurons ameliorates anxiety-like behaviors in single prolonged stress-induced PTSD model rats.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that arises after extremely traumatic events, with clinically significant and lasting impacts on both physical and psychological health. The present study examined the role of ventral tegmental area (VTA) dopaminergic signaling in anxiety-like behaviors and the underlying mechanisms in PTSD model rats. Chemogenetic technology was employed to specifically activate VTA dopamine (DA) neurons in rats subjected to single prolonged stress (SPS), and open field and elevated plus maze tests were applied to evaluate the anxiety-like manifestations. Subsequently, in vivo extracellular electrophysiological analyses were used to examine alterations in the firing characteristics of VTA DA neurons. Chemogenetic activation enhanced the firing and burst rates of VTA DA neurons in SPS-induced PTSD model rats and concomitantly mitigated the anxiety-like behavioral phenotypes. Collectively, these findings reveal a direct association between PTSD-relevant anxiety behaviors and VTA dopaminergic activity, and further suggest that interventions designed to enhance VTA dopaminergic activity may be a potential strategy for PTSD treatment.

Arecoline Induces an Excitatory Response in Ventral Tegmental Area Dopaminergic Neurons in Anesthetized Rats.

Arecoline is the principle psychoactive alkaloid in areca nuts. Areca nuts are chewable seeds of Areca catechu L., which are epidemic plants that grow in tropical and subtropical countries and cause dependency after long-term use. However, the mechanisms underlying such dependency remain largely unclear, and therefore, no effective interventions for its cessation have been developed. The present study aimed to examine the effects of arecoline on neurons of the ventral tegmental area (VTA). After rats were anesthetized and craniotomized, electrophysiological electrodes were lowered into the VTA to obtain extracellular recordings. The mean firing rate of dopaminergic and GABAergic neurons were then calculated and analyzed before and after arecoline treatment. The burst characteristics of the dopaminergic neurons were also analyzed. The results showed that arecoline evoked a significant enhancement of the firing rate of dopaminergic neurons, but not GABAergic neurons. Moreover, arecoline evoked remarkable burst firings in the dopaminergic neurons, including an increase in the burst rate, elongation in the burst duration, and an enhancement in the number of spikes per burst. Collectively, the findings revealed that arecoline significantly excited VTA dopaminergic neurons, which may be a mechanism underlying areca nut dependency and a potential target for areca nut cessation therapy.

Ventral Tegmental Area Dysfunction and Disruption of Dopaminergic Homeostasis: Implications for Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition characterized by intrusive recollections of the traumatic event, avoidance behaviors, hyper-arousal to event-related cues, cognitive disruption, and mood dysregulation. Accumulating preclinical and clinical evidence implicates dysfunction of the ventral tegmental area (VTA) dopaminergic system in PTSD pathogenesis. This article reviews recent advances in our knowledge of the relationship between dopaminergic dyshomeostasis and PTSD, including the contributions of specific dopaminergic gene variants to disease susceptibility, alterations in VTA dopamine neuron activity, dysregulation of dopaminergic transmission, and potential pharmacological and psychological interventions for PTSD targeting the dopaminergic system. An in-depth understanding of PTSD etiology is crucial for the development of innovative risk assessment, diagnostic, and treatment strategies following traumatic events.