The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Walter Fratta - One of the best experts on this subject based on the ideXlab platform.
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changed accumbal responsiveness to alcohol in rats pre treated with nicotine or the cannabinoid receptor agonist WIN 55 212 2
Neuroscience Letters, 2008Co-Authors: Jose Antonio Lopezmoreno, Walter Fratta, Maria Scherma, Fernando Rodriguez De Fonseca, Gustavo Gonzalezcuevas, Miguel NavarroAbstract:Alcohol, nicotine, and cannabinoid acutely increase the activity of the mesolimbic dopamine (DA) pathway. Although polysubstance consumption is a common pattern of abuse in humans, little is known about dopamine release folloWINg pre-exposure to these drugs. The purpose of this study was to test whether alcohol-induced dopamine release into the nucleus accumbens (NAc) shell is modified by different pre-treatments: water (i.g.), alcohol (1 g/kg, i.g.), nicotine (0.4 mg/kg, s.c.), and WIN 55,212-2 (1 mg/kg, s.c.). Male Wistar rats were treated (i.g.) for 14 days with either water or alcohol. In the folloWINg 5 days rats were injected (s.c.) with vehicle, nicotine, or WIN 55,212-2. Finally, a cannula was surgically implanted into the NAc shell and alcohol-induced extracellular dopamine release was monitored in freely moving rats. Alcohol (1 g/kg; i.g.) only increased the release of dopamine when animals were previously treated with water. This DA increase was markedly inhibited by (subchronic) treatment (5 days) with nicotine or WIN 55-212-2 as well as by previous (chronic) exposure to alcohol (14 days). These data demonstrate that pre-treatment with nicotine and the cannabinoid agonist WIN 55,212-2 is able to change the sensitivity of the NAc shell in response to a moderate dose of alcohol. Therefore, cannabinoid and nicotine exposure may have important implications on the rewarding effects of alcohol, because these drugs lead to long-lasting changes in accumbal dopamine transmission.
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bidirectional regulation of mu opioid and cb1 cannabinoid receptor in rats self administering heroin or WIN 55 212 2
European Journal of Neuroscience, 2007Co-Authors: Liana Fattore, Walter Fratta, Daniela Vigano, Paola Fadda, Tiziana Rubino, Daniela ParolaroAbstract:This study examines the effect of intravenous self-administration (SA) of either heroin or the cannabinoid receptor agonist WIN 55,212-2 on levels and functionality of l-opioid (MOR) and CB1-cannabinoid receptors (CB1R) in reward-related brain areas, such as the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (Hippo), amygdala (Amy), hypothalamus (Hypo) and ventral tegmental area (VTA). [ 3 H]DAMGO and [ 3 H]CP-55,940 autoradiography and agonist-stimulated [ 35 S]GTPcS binding were performed on brain sections of rats firmly self-administering heroin or WIN 55,212-2. Animals failing to
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intravenous self administration of the cannabinoid cb1 receptor agonist WIN 55 212 2 in rats
Psychopharmacology, 2001Co-Authors: Liana Fattore, Cristina M Martellotta, Giancarlo Cossu, Walter FrattaAbstract:Rationale: Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A. Objective: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 µg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. Results: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 µg/kg per injection. Response rate increased folloWINg pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished folloWINg both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. Conclusion: Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus alloWINg further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.
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cb1 cannabinoid receptor agonist WIN 55 212 2 decreases intravenous cocaine self administration in rats
Behavioural Brain Research, 1999Co-Authors: Liana Fattore, Cristina M Martellotta, Giancarlo Cossu, Stefania M Mascia, Walter FrattaAbstract:The effect of the CB1 cannabinoid receptor agonist WIN 55, 212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55, 212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB1 receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55, 212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB1 cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine.
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self administration of the cannabinoid receptor agonist WIN 55 212 2 in drug naive mice
Neuroscience, 1998Co-Authors: M C Martellotta, Liana Fattore, Giancarlo Cossu, Gian Luigi Gessa, Walter FrattaAbstract:Abstract Marijuana is one of the most widely used illicit recreational drugs. However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased. The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB 1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB 1 receptors.
Jacqueline Sagen - One of the best experts on this subject based on the ideXlab platform.
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sustained antinociceptive effect of cannabinoid receptor agonist WIN 55 212 2 over time in rat model of neuropathic spinal cord injury pain
Journal of Rehabilitation Research and Development, 2009Co-Authors: Aldric Hama, Jacqueline SagenAbstract:A significant complaint associated with spinal cord injury (SCI) is chronic pain, which includes symptoms such as cutaneous hypersensitivity and spontaneous unevoked pain and is difficult to treat with currently available drugs. One complication with current analgesics is tolerance, a decrease in efficacy with repeated treatment over time. One promising class of pharmacological treatment is cannabinoid (CB) receptor agonists. The current study assessed the efficacy of the CB receptor agonist WIN 55,212-2 (WIN) in a rat model of neuropathic SCI pain. Brief spinal compression leads to significant hindpaw hypersensitivity to tactile stimulation. WIN dose-dependently increased withdrawal thresholds and continued to demonstrate efficacy over a twice-daily 7-day treatment regimen. By contrast, the efficacy of morphine in SCI rats decreased over the same treatment period. Similarly, the antinociceptive efficacy of WIN to acute noxious heat in uninjured rats diminished over time. These data suggest that the sustained efficacy of a CB receptor agonist for pain could depend on the pain state. Such agonists may hold promise for long-term use in alleviating chronic SCI pain.
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antinociceptive effect of cannabinoid agonist WIN 55 212 2 in rats with a spinal cord injury
Experimental Neurology, 2007Co-Authors: Aldric Hama, Jacqueline SagenAbstract:Abstract Spinal cord injury (SCI) pain exhibits many symptoms associated with peripheral neuropathic pain, including increased tactile hypersensitivity. One novel approach to ameliorate SCI pain is the use of cannabinoid (CB) ligands. The current study evaluated the efficacy of the nonselective CB receptor agonist WIN 55,212-2 on tactile hypersensitivity in rats folloWINg a brief compression to the thoracic spinal cord. The withdrawal thresholds of the hind paws folloWINg SCI were significantly decreased, indicating tactile hypersensitivity. Systemic injection of WIN 55,212-2 increased withdrawal thresholds in a dose-dependent manner. Pretreatment with the CB1 receptor subtype-selective antagonist AM 251 completely abolished the antinociceptive effect of WIN 55,212-2 whereas pretreatment with the CB2 receptor subtype-selective antagonist AM 630 did not alter the antinociceptive effect of WIN 55,212-2. These data indicate that a CB1-selective agonist may be novel therapeutic treatment for clinical SCI pain.
Liana Fattore - One of the best experts on this subject based on the ideXlab platform.
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bidirectional regulation of mu opioid and cb1 cannabinoid receptor in rats self administering heroin or WIN 55 212 2
European Journal of Neuroscience, 2007Co-Authors: Liana Fattore, Walter Fratta, Daniela Vigano, Paola Fadda, Tiziana Rubino, Daniela ParolaroAbstract:This study examines the effect of intravenous self-administration (SA) of either heroin or the cannabinoid receptor agonist WIN 55,212-2 on levels and functionality of l-opioid (MOR) and CB1-cannabinoid receptors (CB1R) in reward-related brain areas, such as the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CP), hippocampus (Hippo), amygdala (Amy), hypothalamus (Hypo) and ventral tegmental area (VTA). [ 3 H]DAMGO and [ 3 H]CP-55,940 autoradiography and agonist-stimulated [ 35 S]GTPcS binding were performed on brain sections of rats firmly self-administering heroin or WIN 55,212-2. Animals failing to
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intravenous self administration of the cannabinoid cb1 receptor agonist WIN 55 212 2 in rats
Psychopharmacology, 2001Co-Authors: Liana Fattore, Cristina M Martellotta, Giancarlo Cossu, Walter FrattaAbstract:Rationale: Δ9-Tetrahydrocannabinol (Δ9-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB1 receptor antagonist SR 141716A. Objective: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 µg/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB1 receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. Results: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 µg/kg per injection. Response rate increased folloWINg pretreatment with the specific CB1 receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished folloWINg both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. Conclusion: Rats will intravenously self-administer the synthetic CB1 receptor agonist WIN 55,212-2 under specific experimental conditions, thus alloWINg further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour.
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cb1 cannabinoid receptor agonist WIN 55 212 2 decreases intravenous cocaine self administration in rats
Behavioural Brain Research, 1999Co-Authors: Liana Fattore, Cristina M Martellotta, Giancarlo Cossu, Stefania M Mascia, Walter FrattaAbstract:The effect of the CB1 cannabinoid receptor agonist WIN 55, 212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55, 212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB1 receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55, 212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB1 cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine.
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self administration of the cannabinoid receptor agonist WIN 55 212 2 in drug naive mice
Neuroscience, 1998Co-Authors: M C Martellotta, Liana Fattore, Giancarlo Cossu, Gian Luigi Gessa, Walter FrattaAbstract:Abstract Marijuana is one of the most widely used illicit recreational drugs. However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased. The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB 1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB 1 receptors.
Aldric Hama - One of the best experts on this subject based on the ideXlab platform.
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sustained antinociceptive effect of cannabinoid receptor agonist WIN 55 212 2 over time in rat model of neuropathic spinal cord injury pain
Journal of Rehabilitation Research and Development, 2009Co-Authors: Aldric Hama, Jacqueline SagenAbstract:A significant complaint associated with spinal cord injury (SCI) is chronic pain, which includes symptoms such as cutaneous hypersensitivity and spontaneous unevoked pain and is difficult to treat with currently available drugs. One complication with current analgesics is tolerance, a decrease in efficacy with repeated treatment over time. One promising class of pharmacological treatment is cannabinoid (CB) receptor agonists. The current study assessed the efficacy of the CB receptor agonist WIN 55,212-2 (WIN) in a rat model of neuropathic SCI pain. Brief spinal compression leads to significant hindpaw hypersensitivity to tactile stimulation. WIN dose-dependently increased withdrawal thresholds and continued to demonstrate efficacy over a twice-daily 7-day treatment regimen. By contrast, the efficacy of morphine in SCI rats decreased over the same treatment period. Similarly, the antinociceptive efficacy of WIN to acute noxious heat in uninjured rats diminished over time. These data suggest that the sustained efficacy of a CB receptor agonist for pain could depend on the pain state. Such agonists may hold promise for long-term use in alleviating chronic SCI pain.
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antinociceptive effect of cannabinoid agonist WIN 55 212 2 in rats with a spinal cord injury
Experimental Neurology, 2007Co-Authors: Aldric Hama, Jacqueline SagenAbstract:Abstract Spinal cord injury (SCI) pain exhibits many symptoms associated with peripheral neuropathic pain, including increased tactile hypersensitivity. One novel approach to ameliorate SCI pain is the use of cannabinoid (CB) ligands. The current study evaluated the efficacy of the nonselective CB receptor agonist WIN 55,212-2 on tactile hypersensitivity in rats folloWINg a brief compression to the thoracic spinal cord. The withdrawal thresholds of the hind paws folloWINg SCI were significantly decreased, indicating tactile hypersensitivity. Systemic injection of WIN 55,212-2 increased withdrawal thresholds in a dose-dependent manner. Pretreatment with the CB1 receptor subtype-selective antagonist AM 251 completely abolished the antinociceptive effect of WIN 55,212-2 whereas pretreatment with the CB2 receptor subtype-selective antagonist AM 630 did not alter the antinociceptive effect of WIN 55,212-2. These data indicate that a CB1-selective agonist may be novel therapeutic treatment for clinical SCI pain.
Cezary Szczylik - One of the best experts on this subject based on the ideXlab platform.
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involvement of the cb2 cannabinoid receptor in cell growth inhibition and g0 g1 cell cycle arrest via the cannabinoid agonist WIN 55 212 2 in renal cell carcinoma
BMC Cancer, 2018Co-Authors: Mohammed I Khan, Anna A Sobocinska, Klaudia K Brodaczewska, Katarzyna Zielniok, Malgorzata Gajewska, Claudine Kieda, Anna M Czarnecka, Cezary SzczylikAbstract:The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212–2 (WIN-55)] in RCC cell lines. Human RCC cell lines were used for this study. The CB 1 and CB 2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB1 and CB2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells. The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis. This study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed.
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Involvement of the CB2 cannabinoid receptor in cell growth inhibition and G0/G1 cell cycle arrest via the cannabinoid agonist WIN 55,212–2 in renal cell carcinoma
BMC, 2018Co-Authors: Mohammed I Khan, Anna A Sobocinska, Klaudia K Brodaczewska, Katarzyna Zielniok, Malgorzata Gajewska, Claudine Kieda, Anna M Czarnecka, Cezary SzczylikAbstract:Abstract Background The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212–2 (WIN-55)] in RCC cell lines. Methods Human RCC cell lines were used for this study. The CB 1 and CB 2 gene expression levels were analyzed using real-time PCR. Flow cytometric, immunocytochemical and western blot analyses were performed to confirm CB1 and CB2 receptor protein expression. The anti-proliferative effects of synthetic cannabinoids were investigated on cell viability assay. The CB1 and CB2 receptors were blocked pharmacologically with the antagonists SR141716A and AM-630, respectively, to investigate the effects of the agonists JWH-133 and WIN-55. Cell cycle, apoptosis and LDH-based cytotoxicity were analyzed on cannabinoid-treated RCC cells. Results The CB1 and CB2 genes expression was shown by real-time PCR and flow cytometric and western blot analysis indicating a higher level of CB2 receptor as compared to CB1 in RCC cells. Immunocytochemical staining also confirmed the expression of the CB1 and CB2 proteins. We also found that the synthetic cannabinoid agonist WIN-55 exerted anti-proliferative and cytotoxic effects by inhibiting the growth of RCC cell lines, while the CB2 agonist JWH-133 did not. Pharmacologically blocking the CB1 and CB2 receptors with their respective antagonists SR141716A and AM-630, followed by the WIN-55 treatment of RCC cells allowed uncovering the involvement of CB2, which led to an arrest in the G0/G1 phase of the cell cycle and apoptosis. Conclusions This study elucidated the involvement of CB2 in the in vitro inhibition of RCC cells, and future applications of CB2 agonists in the prevention and management of RCC are discussed
