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It has been reported that environmental stimuli can positively influence addictive responses and the pharmacological effects of drugs of abuse. In this work, we evaluated the ability of environmental enrichment (EE) to attenuate addictive behaviours in mice after repeated exposure to toluene. We also analysed the role of D1 receptors (D1R) in animals chronically exposed to toluene and in those housed under EE. Mice (Swiss Webster) were exposed to toluene (0, 2000 or 4000 ppm, 30 min a day), and addictive responses were examined in the behavioural sensitization model. The induction of sensitization was evaluated over 4 weeks, and its expression was assessed in animals repeatedly exposed to toluene (0 or 4000 ppm, 30 min a day/4 weeks) and then housed under EE conditions during 4 more weeks. D1R levels were measured under these two experimental conditions in the prefrontal cortex, nucleus accumbens, hippocampus and caudate. The results showed that D1R levels decreased during toluene-induced behavioural sensitization. An increase in D1R levels was found in animals housed in EE conditions, in addition to the attenuated expression of behavioural sensitization. These results indicate that environmental stimulation attenuates addictive behaviour induced by toluene and that dynamic changes in D1R are linked in this response., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome with various concomitant symptoms like sleep disorders. FM patients are mainly women and menopause might play an important role in the altered processing of somatosensory information. Adverse effects and moderated efficacy of drugs promote treatment discontinuation by patients. Animal models of FM report pain and depression-like behaviors, but none of them have explored sleep disturbance as possible marker in the preclinic diagnostic. The aim of this study was to investigate alterations of the sleep architecture in the reserpine (RES)-induced FM model in ovarectomized (OVX) rats. The behavioral thresholds of nociceptive response in the experimental FM were analyzed in a first block using muscle pressure, tactile response and allodynia to cold stimulus. In a second block, the sleep-wake cycle was examined in a polysomnographic study. Groups (n = 8) consisted in: (a) no treatment, (b) RES vehicle, (c) RES alone, (d) RES + vehicle of fluoxetine (FLX, antidepressant reference drug), and (e) RES + FLX. Our results demonstrated that RES induced pain-related behavior (50-70%) in OVX rats and altered sleep architecture by the increase of total wake time (38%), diminution of the no-REM stage (SWS-I 33% and SWS-II 76%), and abolition of the REM sleep, effects that were partially reverted in the presence of FLX. In conclusion, our results support the face validity of the RES-induced pain-related behavior as FM model showing nociceptive behavioral responses associated to sleep alterations observed as symptoms in FM patients; thus, these evidences substantiate its usefulness to look for alternatives of treatment for FM symptoms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Clinical evidence suggests that there is decreased pain sensitivity in schizophrenia; however, the neurobiological mechanism of this decrease remains unknown. Using functional magnetic resonance imaging, we examined the blood oxygen level-dependent (BOLD) changes induced by experimental pain-tolerance (endure) hot stimuli vs. non-painful stimuli during an acute psychotic episode in 12 drug-free patients with schizophrenia and in 13 gender- and age-matched healthy controls. The analyses revealed that patients showed a greater BOLD response at S1 compared with controls but a reduced BOLD response in the posterior cingulate cortex (PCC), insula, and brainstem during pain-tolerance stimuli. Pain-tolerance temperature was higher in patients than in healthy controls. BOLD response in the insula positively correlated with unpleasantness and temperature in controls, but this effect was not observed in patients. S1 BOLD response positively correlated with unpleasantness in patients but not in controls. These initial results confirm that unmedicated patients with schizophrenia have a higher pain tolerance than controls, decreased activation in pain affective-cognitive processing regions (insula, PCC, brainstem), and an over-activation of the primary sensory-discriminative pain processing region (S1). These pilot results are the first to explore the mechanism driving altered pain sensitivity in schizophrenia., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The clinical relationship between pain and depression has been extensively reported. The purpose of this study was to compare the cerebral blood flow (CBF) of patients with major depressive disorder (MDD) during stimulation with experimental pain tolerance or sham stimulation, before and after 2 weeks of at least partially effective antidepressant treatment (ADT), in order to determine the cerebral regions associated with pain processing in the two clinical states., Methods: Twenty-four antidepressant-free outpatients diagnosed with MDD (DSM-IV), without any pain complaints and a basal score>or=20 points on the Hamilton Rating Scale for Depression were included. Cerebral SPECTs were performed before and after ADT. Patients were stimulated with pain pressure tolerance (PT) or sham stimulation during the radiotracer cerebral uptake time., Results: The comparison between PT and sham stimulation before ADT showed an increase of CBF of PT stimulated patients in right temporal gyrus, left amygdale, right anterior cingulated cortex, bilateral medial frontal gyrus, bilateral insula, lingual gyrus, right precentral gyrus and left postcentral gyrus. Equal comparison after ADT showed an increase of CBF of PT stimulated patients only in left middle frontal gyrus., Limitations: The sample includes exclusively outpatients with mild-moderate depression., Conclusion: CBF before ADT increases in brain areas related with the affective and cognitive components of pain; in contrast, after ADT increases only in cognitive pain related areas. These results offer new avenues to investigate the cerebral substrate of the common relationship between pain and depression.

The effects of electrical stimulation of the ventral tegmental area (VTA) on male rat sexual behaviour were studied. Stimulation of dorsal VTA facilitated copulation of sexually experienced animals; while ventral VTA stimulation inhibited sexual behaviour. In sexually exhausted rats, stimulation at either region lacked of an effect. It is concluded that different loci within the VTA exert opposite influences on male sexual behaviour expression and that copulation to satiation modifies this VTA control.

Toluene is an abused solvent widely used in several commercial products. Recent evidence indicates that this solvent is a non-competitive inhibitor of NMDA receptors. Since NMDA receptors have been implicated in pain, this paper describes studies of the effects of increasing concentrations of inhaled toluene on nociception. Swiss Webster mice were exposed to toluene (500-8000 ppm) in static exposure chambers for 30 min. After completing the exposure period, animals were tested for nociception using the hot plate test. Toluene dose-dependently increased nociception as reflected by shorter latencies for the reflex, paw-lick and escape responses in toluene-treated mice with respect to their controls (animals exposed to air). In order to determine the possible role of opioids in this response, morphine (1-10 mg/kg) was injected before toluene inhalation. Toluene was not able to block morphine-induced antinocieption, however, it produced a shift of the morphine dose-response curve to lower effects, suggesting a physiological antagonism. No potentiation was seen when toluene was administered in combination with naloxone. Present results suggest that toluene increases nociception via neurotransmitter systems others than the glutamatergic.

The ventral tegmental area (VTA) has been traditionally related with the control of motor responses. However, some studies show that this area is also involved in the processing of nociceptive information. It has been reported that this nucleus participates in the dissociative analgesia phenomenon. In the few works where electrical stimulation and lesion of the VTA have been performed, evaluated with persistent or chronic pain related behaviors, contradictory results have been obtained. Thus, a more detailed analysis of the role of the VTA in persistent pain is needed. Two series of experiments were performed: lesions of this nucleus were done with radiofrequency, (bilaterally at two points per side using a temperature range from 50 to 80 degrees C), and the VTA was electrically stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1 s every 5 s) using two different schemes:10 min before the induction of the nociceptive stimulus and 90 min after the induction of the nociceptive stimulus. The latter allowed us to distinguish if the VTA electrical stimulation had a distinctive antinociceptive effect when applied before or after the induction of the nociceptive stimulus on a persistent pain related behavioral response in the rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced the occurrence of SIB; while activation of this same nucleus by electrical stimulation after the nociceptive stimulus, but not before, facilitates the analgesic process, expressed as a 1 day delay in SIB onset. These results indicate that the VTA is a brain structure that plays a key role in the processing and modulation of persistent pain information. Data are discussed in terms of the relationship of the VTA with the affective component of pain.

Oral administration of aqueous red pepper (Capsicum frutescens, Cf) solution and low capsaicin (8-methyl-N-vanillyl-6-nonenamide) doses during gestation produces an increase in the latency of the thermonociceptive escape response of rat offspring. The present work shows that different amounts of Cf (10%, 25% and 50%) incorporated to normal food of gestating rats modify in a dose-dependent manner the flexion reflex latency (R), as well as the latency of appearance of antialgesic behaviours expressed as paw lick (P) and escape response (E) using the hot plate test (53 degrees C+/-0.5 degrees C). The latency of the same parameters was tested in the same subjects 55 days later to determine the persistence of this effect. Results show an increase in latency of the three parameters R, P and E in all experimental groups with respect to controls. Animals (Cf, 25% group) tested 55 days after the first test exhibited latencies similar to controls, which suggests that the process is reversible.