Combination of low doses of mirtazapine plus venlafaxine produces antidepressant-like effects in rats, without affecting male or female sexual behavior.

Rationale: Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans.

Effect of exercise duration on toluene-induced locomotor sensitization in mice: a focus on the Renin Angiotensin System.

Rationale: Exercise attenuates addictive behavior; however, little is known about the contribution of exercise duration to this positive effect. The Renin Angiotensin System (RAS) has been implicated both in addictive responses and in the beneficial effects of exercise; though, its role in the advantageous effects of exercise on toluene-induced addictive responses has not been explored.

Objectives: To evaluate the impact of different exercise regimens in mitigating the expression of toluene-induced locomotor sensitization and to analyze changes in RAS elements' expression at the mesocorticolimbic system after repeated toluene exposure and following voluntary wheel running in toluene-sensitized animals.

The endocrine disruptor DE-79 alters oxytocinergic transmission and sexual behavior expression in male rats.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants are persistent organic pollutants exerting important health effects. PBDEs with >5 bromide substitutions were considered less harmful and therefore extensively used commercially. DE-79 was a widely used PBDE mixture of hexa-, hepta-, octa- and nona-brominated compounds that increases vasopressin (AVP) production.

: Drug of Abuse and Therapeutic Agent, Two Sides of the Same Coin.

The consumption of plant, known as marijuana in the Western world, for different purposes (therapeutic, intoxicating, and spiritual) due to its psychoactive effects, can be traced back to ancient times. is the most used illicit drug worldwide; however, its legal status is changing rapidly. regulation will allow a better understanding of its effects as a misused drug, including new challenges, such as the availability of highly potent .

The endogenous cannabinoid system modulates male sexual behavior expression.

The endocannabinoid system (ECS) plays a key neuromodulatory role in the brain. Main features of endocannabinoids (eCBs) are that they are produced on demand, in response to enhanced neuronal activity, act as retrograde messengers, and participate in the induction of brain plasticity processes. Sexual activity is a motivated behavior and therefore, the mesolimbic dopaminergic system (MSL) plays a central role in the control of its appetitive component (drive to engage in copulation).

Endocannabinoid modulation of allergic responses: Focus on the control of FcεRI-mediated mast cell activation.

Allergic reactions are highly prevalent pathologies initiated by the production of IgE antibodies against harmless antigens (allergens) and the activation of the high-affinity IgE receptor (FcεRI) expressed in the surface of basophils and mast cells (MCs). Research on the mechanisms of negative control of those exacerbated inflammatory reactions has been intense in recent years. Endocannabinoids (eCBs) show important regulatory effects on MC-mediated immune responses, mainly inhibiting the production of pro-inflammatory mediators.

Sexual satiety modifies methamphetamine-induced locomotor and rewarding effects and dopamine-related protein levels in the striatum of male rats.

Rationale: Drug and natural rewarding stimuli activate the mesolimbic dopaminergic system. Both methamphetamine (Meth) and copulation to satiety importantly increase dopamine (DA) release in the nucleus accumbens (NAc), but with differences in magnitude. This paper analyzes the interaction between Meth administration and the intense sexual activity associated with sexual satiety.

The nucleus accumbens dopamine increase, typically triggered by sexual stimuli in male rats, is no longer produced when animals are sexually inhibited due to sexual satiety.

Rationale: Exposure of male rats to an inaccessible receptive female and copulation increases dopamine (DA) levels in the nucleus accumbens (NAcc). Males copulating to satiety become sexually inhibited and most of them do not display sexual activity when presented with a sexually receptive female 24 h later. This inhibitory state can be pharmacologically reversed.

Mast cells and histamine are involved in the neuronal damage observed in a quinolinic acid-induced model of Huntington's disease.

Huntington´s disease (HD) is a pathological condition that can be studied in mice by the administration of quinolinic acid (QUIN), an agonist of the N-methyl-d-aspartate receptor (NMDAR) that induces NMDAR-mediated cytotoxicity and neuroinflammation. Mast cells (MCs) participate in numerous inflammatory processes through the release of important amounts of histamine (HA). In this study, we aimed to characterize the participation of MCs and HA in the establishment of neural and oxidative damage in the QUIN-induced model of HD.

Endocannabinoids Released in the Ventral Tegmental Area During Copulation to Satiety Modulate Changes in Glutamate Receptors Associated With Synaptic Plasticity Processes.

Endocannabinoids modulate mesolimbic (MSL) dopamine (DA) neurons firing at the ventral tegmental area (VTA). These neurons are activated by copulation, increasing DA release in nucleus accumbens (NAcc). Copulation to satiety in male rats implies repeated ejaculation within a short period (around 2.

Endocannabinoids mediate long-lasting behavioural and physiological changes in male rats induced by the repeated activation of the mesolimbic system by copulation to satiety.

Sexually satiated male rats exhibit long-lasting physiological changes, suggestive of brain plasticity, the most conspicuous of which are a sexual behaviour inhibition and a generalised drug hypersensitivity. Copulation activates the mesolimbic circuit increasing dopamine (DA) release in the nucleus accumbens (NAcc) and, enhanced midbrain DA neuron activity promotes endocannabinoid (eCB) release in the ventral tegmental area (VTA). The objective of this work was to explore the possible participation of DA and/or eCB transmission in the induction of these two long-lasting phenomena.

Endocannabinoids Interact With the Dopaminergic System to Increase Sexual Motivation: Lessons From the Sexual Satiety Phenomenon.

In male rats, copulation to satiety induces a long-lasting sexual inhibitory state, considered to rely on a decreased sexual motivation. Dopaminergic transmission at the mesolimbic system plays a central role in the regulation of male sexual motivation. Endocannabinoids (eCBs) modulate the activity of the mesolimbic system and both dopamine (DA) and cannabinoid receptor activation reverses the sexual inhibition that characterizes sexually satiated rats.

TLR4 Receptor Induces 2-AG-Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells.

Mast cells (MCs) contribute to the control of local inflammatory reactions and become hyporesponsive after prolonged TLR4 activation by bacterial LPS. The molecular mechanisms involved in endotoxin tolerance (ET) induction in MCs are not fully understood. In this study, we demonstrate that the endocannabinoid 2-arachidonoylglycerol (2-AG) and its receptor, cannabinoid receptor 2 (CB2), play a role in the establishment of ET in bone marrow-derived MCs from C57BL/6J mice.

Nucleus accumbens dopamine increases sexual motivation in sexually satiated male rats.

Rationale: The influence of the main dopaminergic brain regions controlling copulation, the medial preoptic area (mPOA) and the nucleus accumbens (NAcc), on male rat sexual behavior expression has not been fully established.

Objective: This work analyzes the sexual effects of dopamine (DA) receptor activation in the mPOA or the NAcc of sexually active male rats, with an intact (sexually experienced) or a reduced (sexually exhausted) sexual motivation.

Methods: The non-specific DA receptor agonist apomorphine and the D2-like receptor agonist quinpirole were infused into the mPOA or the NAcc of sexually experienced or sexually exhausted male rats and their sexual behavior recorded.

Sexual interaction is essential for the transformation of non-copulating rats into sexually active animals by the endocannabinoid anandamide.

The endocannabinoid anandamide (AEA) transforms half of the population of previously non-copulating (NC) rats into sexually active animals in a long-lasting manner. The aim of this work was to explore the nature of this transformation. We identified the dose range in which AEA induces mating behavior in previously NC rats, which evidenced a dose-based, biphasic profile for AEA to induce the transformation of NC rats.

Sexual behaviour is impaired by the abused inhalant toluene in adolescent male rats.

Inhalant misuse is a worldwide problem, especially among adolescents. Toluene is the most widely misused inhalant. One hallmark of adolescence is the emergence of sexual behaviour, which can be affected by drug use.

Opioid receptor and β-arrestin2 densities and distribution change after sexual experience in the ventral tegmental area of male rats.

Sexual experience modifies brain functioning and copulatory efficiency. Sexual activity, ejaculation in particular, is a rewarding behavior associated with the release of endogenous opioids, which modulate the activity of the mesolimbic dopaminergic system (MLS). In sexually exhausted rats, repeated ejaculation produces μ (MOR) and δ opioid receptor (DOR) internalization in ventral tegmental area (VTA) neurons, as well as long-lasting behavioral changes suggestive of brain plasticity processes.

A new role for GABAergic transmission in the control of male rat sexual behavior expression.

GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABA receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display.

Intra-VTA anandamide infusion produces dose-based biphasic effects on male rat sexual behavior expression.

Sexual behavior is a natural reward and the mesolimbic (MSL) system is involved in the processing of its motivational component and reinforcing properties. Endocannabinoids control rewarding behaviors through the modulation of MSL system's activity. The endocannabinoid anandamide (AEA), systemically administered, produces dose-based, biphasic effects on male rat copulation, facilitating its expression at low doses in both, sexually experienced and sexually exhausted male rats.

Biphasic effects of anandamide on behavioural responses: emphasis on copulatory behaviour.

Endocannabinoids have emerged as important modulators of different neurotransmitter systems in the brain by acting as retrograde messengers. They are released from postsynaptic cell bodies, travel backwards across the synapsis and bind to their receptors located at the presynaptic terminal to inhibit neurotransmitter release. The fatty acid amide, arachidonoylethanolamide (anandamide), is an important endogenous ligand of the G-protein-coupled cannabinoid receptors CB1 and CB2.

Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: possible relevance for human lifelong delayed ejaculation disorder.

Introduction: The sexually sluggish (SLG) male rat has been proposed as an animal model for the study of lifelong delayed ejaculation, a sexual dysfunction for which no treatment is available. Low endocannabinoid anandamide (AEA) doses facilitate sexual behavior display in normal sexually active and in noncopulating male rats through the activation of CB1 receptors.

Aim: To establish whether low AEA doses reduced the ejaculatory threshold of SLG male rats by acting at CB1 receptors.

Glutamatergic transmission is involved in the long lasting sexual inhibition of sexually exhausted male rats.

Copulation to satiation induces a series of enduring physiological changes in male rats, with the appearance of a long lasting sexual inhibitory period as the most conspicuous, that are suggestive of the occurrence of neuroplastic changes. Copulation is a natural reward activating the mesocorticolimbic circuit and inducing nucleus accumbens dopamine release. The repeated activation of this system by drug rewards induces neuroplastic changes involving both dopamine and glutamate transmission.

Dopamine receptors play distinct roles in sexual behavior expression of rats with a different sexual motivational tone.

Dopamine (DA) plays a central role in the expression of male sexual behavior. The effects of DA-enhancing drugs on copulation seem to vary depending on the dose of the agonist used, the type of DA receptor activated, and the sexual condition of the animals. The aim of the present study was to carry out a systematic analysis of the effects of dopaminergic agonists on the expression of male sexual behavior by sexually competent rats in different sexual motivational states, that is when sexually active (sexually experienced) and when temporarily inhibited (sexually exhausted).

Low anandamide doses facilitate male rat sexual behaviour through the activation of CB1 receptors.

Rationale: Endocannabinoids (eCN) exert biphasic effects on several behaviours; however, they have only been reported to inhibit male sexual behaviour. eCN, the endogenous ligands for CB1 receptors, are released in response to neuronal stimulation and regulate the functioning of the mesocorticolimbic system (MCL), which is activated by male sexual behaviour. We hypothesised that eCN might exert biphasic effects on male rat copulatory behaviour and be released during copulation to satiation as a result of the repeated activation of the MCL system.