Molecular Neurobiology
May 2019
Maria E Secci, Paola Mascia, Claudia Sagheddu et al.
The reinforcing effects of Δ9-tetrahydrocannabinol (THC) in rats and monkeys, and the reinforcement-related dopamine-releasing effects of THC in rats, can be attenuated by increasing endogenous levels of kynurenic acid (KYNA) through systemic administration of the kynurenine 3-monooxygenase inhibitor, Ro 61-8048. KYNA is a negative allosteric modulator of α7 nicotinic acetylcholine receptors...
Nature Neuroscience
November 2013
Zuzana Justinova, Paola Mascia, Hui-Qiu Wu et al.
In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates...
British Journal of Pharmacology
October 12, 2013
Charles W. Schindler, Eric B. Thorndike, Bruce E. Blough et al.
35 citations
Background and Purpose The cardiovascular effects produced by 3,4‐methylenedioxymethamphetamine ( MDMA ; ‘ E cstasy’) contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Experimental Approach Radiotelemetry was employed to evaluate the...
British Journal of Pharmacology
April 2012
Leigh V Panlilio, Sergi Ferré, Sevil Yasar et al.
Cannabis and caffeine are two of the most widely used psychoactive substances. Δ(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate...
The FASEB Journal
April 1, 2012
Charles W. Schindler, Michael H Baumann, Eric B. Thorndike et al.
The abuse of MDMA (Ecstasy) peaked in the early 2000s, yet reports of MDMA use from emergency room admission data continue to increase. The potential for cardiovascular effects of MDMA to contribute to its acute toxicity has long been recognized. However, the role of MDMA metabolites in mediating the drug's cardiovascular actions has not been studied. Here we employed radiotelemetry to evaluate...
Addiction Biology
July 2011
Zuzana Justinova, Sergi Ferré, Godfrey H Redhi et al.
Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB(1) receptor ligand anandamide...
Psychopharmacology
April 2010
Marcello Solinas, Gianluigi Tanda, Carrie E Wertheim et al.
Although delta-9-tetreahydrocannabinol (THC)-induced elevations in accumbal dopamine levels are believed to play an important role in the abuse-related effects of cannabis, little direct evidence has been provided that the dopaminergic system is involved in the psychotropic effects of THC. The objective of this study is to investigate whether drugs activating or blocking the dopaminergic system...
Pharmacological Research
November 2007
Marcello Solinas, Sevil Yasar, Steven R Goldberg
Cannabis is the most commonly abused illegal drug in the world and its main psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), produces rewarding effects in humans and non-human primates. Over the last several decades, an endogenous system comprised of cannabinoid receptors, endogenous ligands for these receptors and enzymes responsible for the synthesis and degradation of these...
Journal of Pharmacology and Experimental Therapeutics
June 2007
Marcello Solinas, Maria Scherma, Gianluigi Tanda et al.
Systemic administration of the main active ingredient in cannabis, Delta9-tetrahydrocannabinol (THC), alters extracellular levels of acetylcholine in several brain areas, suggesting an involvement of the cholinergic system in the psychotropic effects of cannabis. Here, we investigated whether drugs acting at either nicotinic or muscarinic receptors can modulate the discriminative effects of...
Journal of Pharmacology and Experimental Therapeutics
April 2007
Marcello Solinas, Gianluigi Tanda, Zuzana Justinova et al.
Anandamide is an endogenous ligand for brain cannabinoid CB(1) receptors, but its behavioral effects are difficult to measure due to rapid inactivation. Here we used a drug-discrimination procedure to test the hypothesis that anandamide, given i.v. or i.p., would produce discriminative effects like those of delta-9-tetrahydrocannabinol (THC) in rats when its metabolic inactivation was...
Psychopharmacology
June 2005
Marcello Solinas, Steven R Goldberg
Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems. To investigate opioid receptor subtypes involved in the discriminative effects of THC. Rats trained to discriminate 3 mg/kg i.p. of THC from vehicle using a two-lever operant drug-discrimination procedure, were tested with compounds that bind...
Psychopharmacology
September 2003
Zuzana Justinova, Gianluigi Tanda, Godfrey H Redhi et al.
Interest in therapeutic activities of cannabinoids has been restrained by the fact that they are most often mediated through activation of cannabinoid CB1 receptors, the same receptors that mediate the effects of delta9-tetrahydrocannabinol (THC) and are responsible for the abuse liability of marijuana. Persistent intravenous self-administration of THC by animals was first demonstrated in...