A conceptual framework for queer, black womxn sexual assault survivors: an adaptation of the minoritised stress model.

Queer, Black womxn experience sexual assault at an alarming rate in the USA leading to adverse mental and physical health outcomes in survivors. A synthesis of the literature was conducted to understand their unique lived experiences and needs. This article proposes an adapted Meyer's Minoritised Stress framework to understand salient clinical factors impacting Queer, Black womxn sexual assault survivors, including those associated with multiple minoritised identities: Queer-based trauma, race-based trauma, cultural betrayal trauma, and misogynoir.

Cannabinoid Modulation of Dopamine Release During Motivation, Periodic Reinforcement, Exploratory Behavior, Habit Formation, and Attention.

Motivational and attentional processes energize action sequences to facilitate evolutionary competition and promote behavioral fitness. Decades of neuropharmacology, electrophysiology and electrochemistry research indicate that the mesocorticolimbic DA pathway modulates both motivation and attention. More recently, it was realized that mesocorticolimbic DA function is tightly regulated by the brain's endocannabinoid system and greatly influenced by exogenous cannabinoids-which have been harnessed by humanity for medicinal, ritualistic, and recreational uses for 12,000 years.

Cannabinoids: Emerging developments in neuropsychopharmacology and biological psychiatry.

Cannabinoids from the cannabis plant were one of the earliest psychoactive phytochemicals harnessed by humanity for their medicinal properties and remain one of the most frequently used and misused classes of chemicals in the world. Despite our long-standing history with cannabinoids, much more is said than is known regarding how these molecules influence the brain and behavior. We are in a rapidly evolving discovery phase regarding the neuroscience of cannabinoids.

Chronic cannabinoid exposure produces tolerance to the dopamine releasing effects of WIN 55,212-2 and heroin in adult male rats.

Synthetic cannabinoids were introduced into recreational drug culture in 2008 and quickly became one of the most commonly abused drugs in the United States. The neurobiological consequences resulting from synthetic cannabinoid repeated exposure remain poorly understood. It is possible that a blunted dopamine (DA) response may lead drug users to consume larger quantities to compensate for this form of neurochemical tolerance.

Buprenorphine is a weak dopamine releaser relative to heroin, but its pretreatment attenuates heroin-evoked dopamine release in rats.

Aims: The United States of America is currently in an opioid epidemic. Heroin remains the most lethal opioid option with its death rate increasing by over 500% in the last decade. The rewarding and reinforcing effects of heroin are thought to be mediated by its ability to increase dopamine concentration in the nucleus accumbens shell.

Endocannabinoid modulation of dopamine release during reward seeking, interval timing, and avoidance.

Endocannabinoids (eCBs) are neuromodulators that influence a wide range of neural systems and behaviors. In the current review, we describe our recent research showing how eCBs, particularly 2-arachidonoylglycerol (2-AG), concurrently shape mesolimbic dopamine (DA) release and associated behavior. We will restrict our discussion by emphasizing three distinct behaviors: reward seeking, interval timing, and active avoidance.

A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction.

like all known drugs of abuse, leads to increased dopamine activation within the mesolimbic pathway. Consequent dopamine release within terminal regions of the striatum is a powerful mediator of reward and reinforcement and patterned dopamine release is critical for associative learning processes that are fundamentally involved in addiction. The endocannabinoid system modulates dopamine release at multiple sites, and the receptors, endogenous ligands, and synthetic and metabolic enzymes of the endocannabinoid system may provide key targets for pharmacotherapies to treat disorders of motivation including addiction.

The power of price compels you: Behavioral economic insights into dopamine-based valuation of rewarding and aversively motivated behavior.

The mesocorticolimbic dopamine pathway is generally considered to be a reward pathway. While shortsighted, there is a strong basis for this view of dopamine function. Here, we first describe the role of phasic dopamine release events in reward seeking.

3,4-methylenedioxymethamphetamine (MDMA) impairs the extinction and reconsolidation of fear memory in rats.

Clinical trials have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) paired with psychotherapy is more effective at reducing symptoms of post-traumatic stress disorder (PTSD) than psychotherapy or pharmacotherapy, alone or in combination. The processes through which MDMA acts to enhance psychotherapy are not well understood. Given that fear memories contribute to PTSD symptomology, MDMA could augment psychotherapy by targeting fear memories.

Local GABA Receptor-Mediated Suppression of Dopamine Release within the Nucleus Accumbens.

Benzodiazepines make up a class of psychoactive drugs that act as allosteric co-activators of the inhibitory GABA receptor. These drugs are useful for the treatment of several psychiatric disorders but also hold considerable abuse liability. Despite the common use and misuse of benzodiazepines, the mechanisms through which these drugs exert their reinforcing effects remain incompletely understood.

Phasic Dopamine Signals in the Nucleus Accumbens that Cause Active Avoidance Require Endocannabinoid Mobilization in the Midbrain.

Phasic dopamine (DA) release accompanies approach toward appetitive cues. However, a role for DA in the active avoidance of negative events remains undetermined. Warning signals informing footshock avoidance are associated with accumbal DA release, whereas depression of DA is observed with unavoidable footshock.

A transient dopamine signal encodes subjective value and causally influences demand in an economic context.

The mesolimbic dopamine system is strongly implicated in motivational processes. Currently accepted theories suggest that transient mesolimbic dopamine release events energize reward seeking and encode reward value. During the pursuit of reward, critical associations are formed between the reward and cues that predict its availability.

Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of Transient Dopamine Release Events in the Nucleus Accumbens.

Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in susceptible individuals. Although it is well established that all drugs of abuse increase brain dopamine levels, and benzodiazepines are allosteric modulators of the GABA receptor, it remains unclear how they alter dopamine release. Using in vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the frequency and amplitude of transient dopamine release events.

Acute Depletion of D2 Receptors from the Rat Substantia Nigra Alters Dopamine Kinetics in the Dorsal Striatum and Drug Responsivity.

Recent studies have used conditional knockout mice to selectively delete the D2 autoreceptor; however, these approaches result in global deletion of D2 autoreceptors early in development. The present study takes a different approach using RNA interference (RNAi) to knockdown the expression of the D2 receptors (D2R) in the substantia nigra (SN), including dopaminergic neurons, which project primarily to the dorsal striatum (dStr) in adult rats. This approach restricts the knockdown primarily to nigrostriatal pathways, leaving mesolimbic D2 autoreceptors intact.

A role for phasic dopamine release within the nucleus accumbens in encoding aversion: a review of the neurochemical literature.

Survival is dictated by an organism's fitness in approaching positive stimuli and avoiding harm. While a rich literature outlines a role for mesolimbic dopamine in reward and appetitive behaviors, dopamine's involvement in aversion and avoidance behaviors remains controversial. Debate surrounding dopamine's function in the processing of negative stimuli likely stems from conflicting results reported by single-unit electrophysiological studies.

Cannabinoid receptor activation shifts temporally engendered patterns of dopamine release.

The ability to discern temporally pertinent environmental events is essential for the generation of adaptive behavior in conventional tasks, and our overall survival. Cannabinoids are thought to disrupt temporally controlled behaviors by interfering with dedicated brain timing networks. Cannabinoids also increase dopamine release within the mesolimbic system, a neural pathway generally implicated in timing behavior.

Endocannabinoids promote cocaine-induced impulsivity and its rapid dopaminergic correlates.

Background: Impaired decision making, a hallmark of addiction, is hypothesized to arise from maladaptive plasticity in the mesolimbic dopamine pathway. The endocannabinoid system modulates dopamine activity through activation of cannabinoid type 1 receptors (CB1Rs). Here, we investigated whether impulsive behavior observed following cocaine exposure requires CB1R activation.

Tales from the dark side: do neuromodulators of drug withdrawal require changes in endocannabinoid tone?

Environmental and interoceptive cues are theorized to serve as 'signals' that motivate drug seeking and effects that may be augmented in the withdrawn state. Phasic dopamine release events are observed in the nucleus accumbens in response to such motivational salient stimuli and are thought to be necessary for drug-associated cues to trigger craving. We recently demonstrated how dopamine neurons encode stimuli conditioned to a negative event, as might occur during conditioned withdrawal, and stimuli predicting the avoidance of negative events, as might occur as an addict seeks out drugs to prevent withdrawal.

On the role of subsecond dopamine release in conditioned avoidance.

Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response.

Conditioned contribution of peripheral cocaine actions to cocaine reward and cocaine-seeking.

Cocaine has actions in the peripheral nervous system that reliably precede--and thus predict--its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood-brain barrier, to isolate the peripheral actions of cocaine and determine their central and behavioral effects in animals first trained to lever-press for cocaine hydrochloride (the centrally acting and abused form of the drug).

Cannabinoids and value-based decision making: implications for neurodegenerative disorders.

In recent years, disturbances in cognitive function have been increasingly recognized as important symptomatic phenomena in neurodegenerative diseases, including Parkinson's Disease (PD). Value-based decision making in particular is an important executive cognitive function that is not only impaired in patients with PD, but also shares neural substrates with PD in basal ganglia structures and the dopamine system. Interestingly, the endogenous cannabinoid system modulates dopamine function and subsequently value-based decision making.

Subsecond dopamine release in the nucleus accumbens predicts conditioned punishment and its successful avoidance.

The mesolimbic dopamine system is believed to be a pathway that processes rewarding information. While previous studies have also implicated a general role for dopamine in punishment and its avoidance, the precise nature of subsecond dopamine release during these phenomena remains unknown. Here, we used fast-scan cyclic voltammetry to investigate whether subsecond dopamine release events in the nucleus accumbens encode cues predicting the avoidance of punishment during behavior maintained in a signaled footshock avoidance procedure.

A brain on cannabinoids: the role of dopamine release in reward seeking.

Increases in mesolimbic dopamine transmission are observed when animals are treated with all known drugs of abuse, including cannabis, and to conditioned stimuli predicting their availability. In contrast, decreases in mesolimbic dopamine function are observed during drug withdrawal, including cannabis-withdrawal syndrome. Thus, despite general misconceptions that cannabis is unique from other drugs of abuse, cannabis exerts identical effects on the mesolimbic dopamine system.

Paradoxical effects of the endocannabinoid uptake inhibitor VDM11 on accumbal neural encoding of reward predictive cues.

A growing body of evidence implicates the endocannabinoid (eCB) system in brain reward function. Previous studies show that antagonizing eCB transmission decreases reward-directed behavior and nucleus accumbens (NAc) encoding of reward predictive cues. We, therefore, hypothesized that elevating eCB levels would uniformly facilitate NAc neural encoding of reward predictive cues and reward-directed behavior.