Fentanyl exposure alters rat CB1 receptor expression in the insula, nucleus accumbens and substantia nigra.

Prolonged periods of opioid use have been shown to cause neuroadaptations in the brain's reward circuitry, contributing to addictive behaviors and drug dependence. Recently, considerable focus has been placed on the role of the endocannabinoid system (ECS) and its CB receptors in opioid-driven behaviors. However, opioid-induced neuroadaptations to the ECS remain understudied.

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.

Background: There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction.

The D3 receptor antagonist SR 21502 reduces cue-induced reinstatement of methamphetamine-seeking in rats.

There is as of yet no FDA-approved medication for methamphetamine use disorder. Although dopamine D3 receptor antagonists have been shown to be useful in reducing methamphetamine seeking in animal models their translation to the clinic has been hindered because currently tested compounds can produce dangerously high blood pressure. Thus, it is important to continue to explore other classes of D3 antagonists.

Environmental enrichment facilitates electric barrier induced heroin abstinence after incubation of craving in male and female rats.

Background: Treatment strategies that aim to promote abstinence to heroin use and reduce vulnerability to drug-use resumption are limited in sustainability and long-term efficacy. We have previously shown that environmental enrichment (EE), when implemented after drug self-administration, reduces drug-seeking and promotes abstinence to cocaine and heroin in male rats. Here, we tested the effects of EE on abstinence in an animal conflict model in males and females, and after periods where incubation of craving may occur.

Biodeterioration of stone monuments: Studies on the influence of bioreceptivity on cyanobacterial biofilm growth and on the biocidal efficacy of essential oils in natural hydrogel.

An important field of research is devoted to the development of innovative, sustainable, and safe methodologies to counteract biodeterioration of stone monuments due to the growth of microbial communities. However, besides the biocide's efficacy, it is crucial to consider the features of substrates on which biocides must be applied, to define the so-called bioreceptivity of the lithic faces. In this research five different lithotypes, namely Lecce stone, Travertine, Peperino, Serena stone, and Granite, have been used as substrates for the growth of cyanobacterial biofilms.

Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning.

Background: Reward-related learning, where animals form associations between rewards and stimuli (i.e., conditioned stimuli [CS]) that predict or accompany those rewards, is an essential adaptive function for survival.

Environmental enrichment reduces heroin seeking following incubation of craving in both male and female rats.

Background: Contemporary treatments for heroin use disorder demonstrate only limited efficacy when the goals are long term abstinence and prevention of relapse. We have demonstrated that environmental enrichment (EE) reduces cue-induced heroin reinstatement in male rats. The present study is an attempt to extend the "anti-relapse" effects of EE to female rats and to periods where incubation of craving is hypothesized to occur.

Neurobiology of reward-related learning.

A major goal in psychology is to understand how environmental stimuli associated with primary rewards come to function as conditioned stimuli, acquiring the capacity to elicit similar responses to those elicited by primary rewards. Our neurobiological model is predicated on the Hebbian idea that concurrent synaptic activity on the primary reward neural substrate-proposed to be ventral tegmental area (VTA) dopamine (DA) neurons-strengthens the synapses involved. We propose that VTA DA neurons receive both a strong unconditioned stimulus signal (acetylcholine stimulation of DA cells) from the primary reward capable of unconditionally activating DA cells and a weak stimulus signal (glutamate stimulation of DA cells) from the neutral stimulus.

Low-dose polypharmacology targeting dopamine D1 and D3 receptors reduces cue-induced relapse to heroin seeking in rats.

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of coadministration of a D1-receptor partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a "conflict" model of abstinence and cue-induced relapse.

Contrasting effects of adolescent and early-adult ethanol exposure on prelimbic cortical pyramidal neurons.

Background: Adolescence and early-adulthood are vulnerable developmental periods during which binge drinking can have long-lasting effects on brain function. However, little is known about the effects of binge drinking on the pyramidal cells of the prelimbic cortex (PrL) during early and protracted withdrawal periods.

Methods: In the present study, we performed whole-cell patch clamp recordings and dendritic spine staining to examine the intrinsic excitability, spontaneous excitatory post-synaptic currents (sEPSCs), and spine morphology of pyramidal cells in the PrL from rats exposed to chronic intermittent ethanol (CIE) during adolescence or early-adulthood.

CaMKII antagonism in the ventral tegmental area impairs acquisition of conditioned approach learning in rats.

This study investigated the role of calcium/calmodulin-dependent protein kinase II (CaMKII), a protein in the second messenger pathway of NMDA receptors, in the ventral tegmental area (VTA) in the acquisition and performance of conditioned approach learning. Male Long-Evans rats (N = 79) were exposed to 3 (to test acquisition) or 7 (to test performance) conditioning sessions in which they received 30 paired presentations of a light stimulus (CS) and a food pellet (US) on a random time schedule. These conditioning sessions were then followed by one 30-min session without the CS or US and lastly by a CS-only test session, where only the light stimulus was presented (without food) according to the same schedule as the conditioning sessions.

(-)-Stepholidine blocks expression, but not development, of cocaine conditioned place preference in rats.

The purpose of this study was to investigate the effects of (-)-stepholidine (SPD), a compound with dopamine D1 partial agonist and D2/D3 antagonist properties, on the development and expression of cocaine conditioned place preference (CPP). Subjects (N = 65; male Long Evans rats) were tested using a CPP procedure consisting of 3 phases: (1) a 15-min pre-exposure session where animals could explore each compartment freely, (2) eight 30-min conditioning sessions where animals were restricted to one side or the other with cocaine (10 mg/kg) or saline, respectively, on alternating days and (3) a 15-minute preference test session where animals could explore each compartment freely. To test the effects of SPD on expression of cocaine CPP, rats were administered vehicle (distilled water with 20 % DMSO), 10, 15 or 20 mg/kg SPD (intraperitoneally) 30 min prior to the test session.

Aberrations in Incentive Learning and Responding to Heroin in Male Rats After Adolescent or Adult Chronic Binge-Like Alcohol Exposure.

Background And Purpose: Binge drinking is a serious problem among adolescents and young adults despite its adverse consequences on the brain and behavior. One area that remains poorly understood concerns the impact of chronic intermittent ethanol (CIE) exposure on incentive learning.

Methods: Here, we examined the effects of CIE exposure during different developmental stages on conditioned approach and conditioned reward learning in rats experiencing acute or protracted withdrawal from alcohol.

Therapeutic efficacy of environmental enrichment for substance use disorders.

Addiction to drug and alcohol is regarded as a major health problem worldwide for which available treatments show limited effectiveness. The biggest challenge remains to enhance the capacities of interventions to reduce craving, prevent relapse and promote long-term recovery. New strategies to meet these challenges are being explored.

(-)-Stepholidine reduces cue-induced reinstatement of cocaine seeking and cocaine self-administration in rats.

Background: Dopamine receptors are implicated in cocaine reward and seeking. We hypothesize that (-)-stepholidine, a dopamine D1/D2/D3 multi-receptor agent, would be effective in reducing cocaine reward and seeking in an animal model. We investigated the effects of (-)-stepholidine in cue-induced reinstatement of cocaine seeking and cocaine self-administration (reward).

The strength of reward-related learning depends on the degree of activation of ventral tegmental area dopamine neurons.

We tested whether (1) the capacity of a reward-associated conditioned stimulus (CS) to cause conditioned activation of ventral tegmental area (VTA) dopamine (DA) neurons is associated with its capacity to elicit conditioned approach responses and (2) whether the acquisition of these capacities by a CS requires N-methyl-D-aspartate (NMDA) and muscarinic acetylcholine (mACh) receptor stimulation. Rats were trained to emit a conditioned approach response to a light CS that was previously paired with food and were treated systemically with scopolamine (a mACh receptor antagonist) or MK-801 (an NMDA receptor antagonist) either prior to each conditioning session (during which animals experienced paired CS and food presentations) or prior to the conditioned approach (CS-only) test. Brains were harvested after the CS-only test and processed for tyrosine hydroxylase (TH) (DA cells) and c-fos in the VTA.

Dopamine D1 and D3 receptor polypharmacology as a potential treatment approach for substance use disorder.

In the search for efficacious pharmacotherapies to treat cocaine addiction much attention has been given to agents targeting dopamine D1 or D3 receptors because of the involvement of these receptors in drug-related behaviors. D1-like and D3 receptor partial agonists and antagonists have been shown to reduce drug reward, reinstatement of drug seeking and conditioned place preference in rodents and non-human primates. However, translation of these encouraging results to clinical settings has been limited due to a number of factors including toxicity, poor pharmacokinetic properties and extrapyramidal and sedative side effects.

Environmental enrichment facilitates cocaine abstinence in an animal conflict model.

In this study, we sought to discover if housing in an enriched environment (EE) is an efficacious intervention for encouraging abstinence from cocaine seeking in an animal "conflict" model of abstinence. Sixteen Long-Evans rats were trained in 3-h daily sessions to self-administer a cocaine solution (1 mg/kg/infusion) until each demonstrated a stable pattern of drug-seeking. Afterward, half were placed in EE cages equipped with toys, obstacles, and a running wheel, while the other half were given clean, standard laboratory housing.

Blockade of NMDA receptors blocks the acquisition of cocaine conditioned approach in rats.

Conditioned stimuli (CSs) exert motivational effects on both adaptive and pathological reward-related behaviors, including drug taking and seeking. We developed a paradigm that allows us to investigate the neuropharmacology by which previously neutral stimuli acquire the capacity to function as CSs and elicit (intravenous) cocaine conditioned approach and used this paradigm to test the role of NMDA receptor stimulation in the acquisition of cocaine conditioned approach. Rats were injected systemically with the NMDA receptor antagonist, MK-801, before the start of 4 consecutive conditioning sessions, each of which consisted of 20 randomly presented light/tone (CS) presentations paired with cocaine infusion contingent upon nose pokes.

Blockade of muscarinic acetylcholine receptors in the ventral tegmental area blocks the acquisition of reward-related learning.

In the present study we investigated whether stimulation of muscarinic acetylcholine (mACh) receptors in the ventral tegmental area (VTA) plays a role in the acquisition of food-based conditioned approach learning. Rats were exposed to 3 (in Experiment 1) or 7 (in Experiment 2) conditioning sessions in which 30, randomly presented light (CS) presentations were paired with delivery of food pellets (US), followed by one session with no light or food and finally one CS-only test session with only light stimulus presentations. Bilateral microinjections of scopolamine (a mACh receptor antagonist) were made either prior to each conditioning session (Experiment 1; to test effects on acquisition) or prior to the CS-only test (Experiment 2; to test effects on performance of the learned response).

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

Objectives: Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor.

Methods: In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP.

Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats.

Rationale: Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking.

Purpose And Methods: Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats.

Results: The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking.

Endometrial polyp harboring a primary B-cell non-Hodgkin lymphoma: a useful in-office hysteroscopic approach.

A non-menopausal women underwent gynecological evaluation for spotting and menstrual irregularities. After first line gynecological assessments, the patient underwent office hysteroscopy. By using an in-office technique, two isthmic endometrial polyps and one cervical polyp were removed.

Environmental enrichment as a potential intervention for heroin seeking.

Background: Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference.

Methods: In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking.