Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.

Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear.

Presynaptic and Postsynaptic Mesolimbic Dopamine D Receptors Play Distinct Roles in Cocaine Versus Opioid Reward in Mice.

Background: Past research has illuminated pivotal roles of dopamine D receptors (DR) in the rewarding effects of cocaine and opioids. However, the cellular and neural circuit mechanisms that underlie these actions remain unclear.

Methods: We employed Cre-LoxP techniques to selectively delete DR from presynaptic dopamine neurons or postsynaptic dopamine D receptor (DR)-expressing neurons in male and female mice.

β-caryophyllene inhibits heroin self-administration, but does not alter opioid-induced antinociception in rodents.

A growing body of research indicates that β-caryophyllene (BCP), a constituent present in a large number of plants, possesses significant therapeutic properties against CNS disorders, including alcohol and psychostimulant use disorders. However, it is unknown whether BCP has similar therapeutic potential for opioid use disorders. In this study, we found that systemic administration of BCP dose-dependently reduced heroin self-administration in rats under an FR2 schedule of reinforcement and partially blocked heroin-enhanced brain stimulation reward in DAT-cre mice, maintained by optical stimulation of midbrain dopamine neurons at high frequencies.

GPR55 is expressed in glutamate neurons and functionally modulates drug taking and seeking in rats and mice.

G protein-coupled receptor 55 (GPR55) has been thought to be a putative cannabinoid receptor. However, little is known about its functional role in cannabinoid action and substance use disorders. Here we report that GPR55 is predominantly found in glutamate neurons in the brain, and its activation reduces self-administration of cocaine and nicotine in rats and mice.

GPR55 is expressed in glutamate neurons and functionally modulates nicotine taking and seeking in rats and mice.

Cannabis legalization continues to progress in the USA for medical and recreational purposes. G protein-coupled receptor 55 (GPR55) is a putative "CB3" receptor. However, its functional role in cannabinoid action and drug abuse is not explored.

PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice.

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ-tetrahydrocannabinol (Δ-THC) is a PPARγ agonist and some endocannabinoids are natural activators of PPARα and PPARγ. However, little is known regarding their cellular distributions in the brain and functional roles in cannabinoid action.

PPARα and PPARγ are expressed in midbrain dopamine neurons and modulate dopamine- and cannabinoid-mediated behavior in mice.

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate gene expression. Δ -tetrahydrocannabinol (Δ -THC) is a PPARg agonist and some endocannabinoids are natural activators of PPAR and PPARg. Therefore, both the receptors are putative cannabinoid receptors.

Dopamine D/D Receptor Ligands Based on Cariprazine for the Treatment of Psychostimulant Use Disorders That May Be Dual Diagnosed with Affective Disorders.

Highly selective dopamine D receptor (DR) partial agonists/antagonists have been developed for the treatment of psychostimulant use disorders (PSUD). However, none have reached the clinic due to insufficient potency/efficacy or potential cardiotoxicity. Cariprazine, an FDA-approved drug for the treatment of schizophrenia and bipolar disorder, is a high-affinity DR partial agonist ( = 0.

Cannabinoid CB1 Receptors Are Expressed in a Subset of Dopamine Neurons and Underlie Cannabinoid-Induced Aversion, Hypoactivity, and Anxiolytic Effects in Mice.

Cannabinoids modulate dopamine (DA) transmission and DA-related behavior, which has been thought to be mediated initially by activation of cannabinoid CB1 receptors (CB1Rs) on GABA neurons. However, there is no behavioral evidence supporting it. In contrast, here we report that CB1Rs are also expressed in a subset of DA neurons and functionally underlie cannabinoid action in male and female mice.

A red nucleus-VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use.

Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions.

A highly DR-selective and efficacious partial agonist (S)-ABS01-113 compared to its DR-selective antagonist enantiomer (R)-ABS01-113 as potential treatments for opioid use disorder.

The non-medical use of opioids has become a national crisis in the USA. Developing non-opioid pharmacotherapies for controlling this opioid epidemic is urgent. Dopamine D receptor (DR) antagonists and low efficacy partial agonists have shown promising profiles in animal models of opioid use disorders (OUD).

Therapeutic potential of PIMSR, a novel CB1 receptor neutral antagonist, for cocaine use disorder: evidence from preclinical research.

Cannabinoid CB1 receptors (CB1Rs) have been major targets in medication development for the treatment of substance use disorders. However, clinical trials with rimonabant, a CB1R antagonist/inverse agonist, failed due to severe side effects. Here, we evaluated the therapeutic potential of PIMSR, a neutral CB1R antagonist lacking an inverse agonist profile, against cocaine's behavioral effects in experimental animals.

Mixed Land Use Levels in Rural Settlements and Their Influencing Factors: A Case Study of Pingba Village in Chongqing, China.

Mixed land use provides an important means of promoting the intensive and efficient use of land resources and stimulating endogenous development power in rural areas. This paper selected Pingba Village in Chongqing as the research area; the land use status data and the social and economic data on rural settlements in the study area for 2021 were obtained through field visits and interviews. Moreover, the land use types in the rural settlements were subdivided according to the principle of dominant function.

Farmers' Willingness to Gather Homesteads and the Influencing Factors-An Empirical Study of Different Geomorphic Areas in Chongqing.

Research Purpose: to analyze farmers' willingness to gather homestead and its influencing factors, so as to provide decision-making basis for the rational layout of rural homestead.

Methods: questionnaire, logistic model. The results are as follows.

Elevation of Extracellular Glutamate by Blockade of Astrocyte Glutamate Transporters Inhibits Cocaine Reinforcement in Rats via a NMDA-GluN2B Receptor Mechanism.

It is well established that glutamate plays an important role in drug-induced and cue-induced reinstatement of drug seeking. However, the role of glutamate in drug reward is unclear. In this study, we systemically evaluated the effects of multiple glutamate transporter (GLT) inhibitors on extracellular glutamate and dopamine (DA) in the nucleus accumbens (NAc), intravenous cocaine self-administration, intracranial brain-stimulation reward (BSR), and reinstatement of cocaine seeking in male and female rats.

Involvement of the ghrelin system in the maintenance of oxycodone self-administration: converging evidence from endocrine, pharmacologic and transgenic approaches.

Ghrelin, an orexigenic hormone, has emerged as a critical biological substrate implicated in drug reward. However, the response of the ghrelin system to opioid-motivated behaviors and the role of ghrelin in oxycodone self-administration remain to be studied. Here, we investigated the reciprocal interactions between the endogenous ghrelin system and oxycodone self-administration behaviors in rats and the role of the ghrelin system in brain stimulation reward (BSR) driven by optogenetic stimulation of midbrain reward circuits in mice.

Involvement of the ghrelin system in the maintenance and reinstatement of cocaine-motivated behaviors: a role of adrenergic action at peripheral β1 receptors.

Cocaine addiction is a significant medical and public concern. Despite decades of research effort, development of pharmacotherapy for cocaine use disorder remains largely unsuccessful. This may be partially due to insufficient understanding of the complex biological mechanisms involved in the pathophysiology of this disorder.

Synaptic Zn potentiates the effects of cocaine on striatal dopamine neurotransmission and behavior.

Cocaine binds to the dopamine (DA) transporter (DAT) to regulate cocaine reward and seeking behavior. Zinc (Zn) also binds to the DAT, but the in vivo relevance of this interaction is unknown. We found that Zn concentrations in postmortem brain (caudate) tissue from humans who died of cocaine overdose were significantly lower than in control subjects.

β-caryophyllene, an FDA-Approved Food Additive, Inhibits Methamphetamine-Taking and Methamphetamine-Seeking Behaviors Possibly CB2 and Non-CB2 Receptor Mechanisms.

Recent research indicates that brain cannabinoid CB2 receptors are involved in drug reward and addiction. However, it is unclear whether β-caryophyllene (BCP), a natural product with a CB2 receptor agonist profile, has therapeutic effects on methamphetamine (METH) abuse and dependence. In this study, we used animal models of self-administration, electrical brain-stimulation reward (BSR) and microdialysis to explore the effects of BCP on METH-taking and METH-seeking behavior.

Effects of the selective dopamine D receptor antagonist PG01037 on morphine-induced hyperactivity and antinociception in mice.

Recent preclinical studies have reported that pretreatment with the novel and highly-selective dopamine D receptor (DR) antagonists R-VK4-40 or VK4-116 attenuates the abuse-related behavioral effects of oxycodone while enhancing its analgesic properties. However, whether these observed effects are generalizable to the broad class of DR antagonists and/or extend to opioids other than oxycodone has not been extensively explored. The present study sought to assess the impact of pretreatment with another selective DR antagonist, PG01037, on several behavioral effects of morphine in mice.

Cannabinoid CB receptors are expressed in glutamate neurons in the red nucleus and functionally modulate motor behavior in mice.

Cannabinoids produce a number of central nervous system effects via the CB receptor (CBR), including analgesia, antianxiety, anti-reward, hypoactivity and attenuation of opioid-induced respiratory depression. However, the cellular distributions of the CBRs in the brain remain unclear. We have reported that CBRs are expressed in midbrain dopamine (DA) neurons and functionally regulate DA-mediated behavior(s).

Optogenetic brain-stimulation reward: A new procedure to re-evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter-Cre mice.

Despite extensive research, the rewarding effects of cannabinoids are still debated. Here, we used a newly established animal procedure called optogenetic intracranial self-stimulation (ICSS) (oICSS) to re-examine the abuse potential of cannabinoids in mice. A specific adeno-associated viral vector carrying a channelrhodopsin gene was microinjected into the ventral tegmental area (VTA) to express light-sensitive channelrhodopsin in dopamine (DA) neurons of transgenic dopamine transporter (DAT)-Cre mice.

Dissecting the role of CB and CB receptors in cannabinoid reward versus aversion using transgenic CB- and CB-knockout mice.

Cannabinoids produce both rewarding and aversive effects in humans and experimental animals. However, the mechanisms underlying these conflicting findings are unclear. Here we examined the potential involvement of CB and CB receptors in cannabinoid action using transgenic CB-knockout (CB-KO) and CB-knockout (CB-KO) mice.