Δ9-Tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats

Braida, Daniela; Iosuè, Stefania; Pegorini, Simona; Sala, Mariaelvina

doi:10.1016/j.ejphar.2004.10.043

Cited by 138 publications

(125 citation statements)

References 34 publications

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“…Onaivi et al (1990) using the EPM found either an anxiogenic or no effect of THC using a range of doses higher than ours. Previous studies have shown that cannabinoid agonists have a dose-dependent biphasic effect in anxiety-like responses (Onaivi et al, 1990;Rodriguez de Fonseca et al, 1996;Valjent et al, 2002), as already observed for other pharmacological actions induced by cannabinoids (Sanudo-Pena et al, 2000;Sulcova et al, 1998;Braida et al, 2004).…”

Section: Discussionmentioning

confidence: 66%

Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats

Rubino

Sala

Viganò

et al. 2007

Neuropsychopharmacol

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We investigated the effect of low doses of intraperitoneal D 9 -tetrahydrocannabinol (THC) on anxiety behavior in rats using the elevated plus maze (EPM). An anxiolytic effect was obtained in a range of doses between 0.075 and 1.5 mg/kg, the 0.75 dose being the most effective. Pretreatment with the CB1 receptor antagonist AM251 fully reversed THC's effect, suggesting CB1 receptors were involved. In order to elucidate the neuroanatomical substrates underlying the effect of the maximal effective dose of THC, we investigated cFos expression in anxiety-related brain regions (prefrontal cortex, nucleus accumbens, amygdala, and hippocampus) of rats exposed to the EPM. THC significantly lowered the amount of cFos in prefrontal cortex and amygdala without affecting the other cerebral areas. As there is increasing evidence that CREB function regulates anxiety-like behavior in rats, the second biochemical parameter we measured was phosphorylated CREB in the same brain areas. Rats treated with THC showed a significant increase in CREB activation in the prefrontal cortex and hippocampus. In the prefrontal cortex this increased activation was linked to an increase in ERK activation, whereas in the hippocampus there was a drop in the activity of CAMKII, a kinase with inhibitory effect on CREB activation. All these effects were reversed by AM251 pretreatment, suggesting that stimulation of CB1 receptors is fundamental for triggering the biochemical events. Our results suggest that the stimulation of these receptors in the prefrontal cortex, amygdala, and hippocampus with the subsequent activation of different signaling pathways is the first event underlying the effects of cannabinoids on anxious states.

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Section: Discussionmentioning

confidence: 66%

Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats

Rubino

Sala

Viganò

et al. 2007

Neuropsychopharmacol

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123

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“…Similar to anxiolytics, marijuana and THC are also able to attenuate the subjective, generally negative emotional states associated with various arousing and stressful stimuli; this stress-attenuating effect could be another possible contributor to its abuse. Even though some animal studies have shown a conditioned place preference for THC (Lepore et al, 1995;Tanda et al, 2000) and its self-administration (Braida et al, 2004;Panlilio et al, 2007), there is little evidence of its potential to induce physical dependence. Along with its psycho-emotional effects, THC induces numerous physiological effects such as analgesia, hypoactivity, hypotension, and hypothermia (Malone and Taylor, 1998;Varvel et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Behavioral and temperature effects of delta 9-tetrahydrocannabinol in human-relevant doses in rats

Smirnov

Kiyatkin

2008

Brain Research

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Marijuana smoking dramatically alters responses to various environmental stimuli. To study this phenomenon, we assessed how delta-9-tetrahydrocannabinol (THC), a primary psychoactive ingredient of marijuana, affects locomotor and brain (nucleus accumbens or NAcc), muscle and skin temperature responses to natural arousing stimuli (one-min tail-pinch and one-min social interaction with another male rat) and iv cocaine (1 mg/kg) in male rats. THC was administered at three widely varying doses (0.5, 2.0 and 8.0 mg/kg, ip), and the drug-induced changes in basal values and responses to stimuli were compared to those occurring following ip vehicle injections (control). Each stimulus in control conditions caused acute locomotor activation, a prolonged increase in brain and muscle temperature (0.6-1.0°C for 20-50 min) and transient decrease in skin temperature (−0.6°C for 1-3 min). While THC at any dose had a tendency to decrease spontaneous locomotion as well as brain and muscle temperatures, true hypothermia and hypoactivity as well as clearly diminished locomotor and temperature responses to all stimuli were only seen following the largest dose. In this case, temperature decreases in the NAcc were stronger than in the muscle, suggesting metabolic brain inhibition as the primary cause of hypoactivity, hypothermia and hyporesponsiveness. While weaker in strength and without associated vasodilatation, this response pattern is mimicked by general anesthetics, questioning to what extent the hypothermic action of THC is specific (i.e., mediated via endogenous cannabinoid receptors) or non-specific, reflecting drug interaction with membrane lipids or other receptors. In contrast, weaker behavioral and temperature effects of THC at lower doses resemble those of diazepam, whose locomotion-and temperature-decreasing effects are evident only in activated conditions, when rats are moving and basal temperatures are elevated. Keywords brain metabolism; brain and body temperature; cannabinoids natural arousing stimuli; intravenous cocaine; vasoconstriction

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“…For example, the opioid antagonist naltrexone decreased Δ 9 -tetrahydrocannabinol (THC)-induced conditioned place preference (Braida et al 2004) and THC self administration in squirrel monkeys responding under a continuous reinforcement schedule (Justinova et al 2004) whereas THC increased heroin self administration (number of injections and breakpoint) in rats responding under a progressive ratio schedule . Conversely, the cannabinoid CB1 receptor antagonist SR-141716A decreased heroin self administration in rats responding under a progressive ratio schedule and either decreased (Navarro et al 2001) or had no effect (Solinas et al 2003) on heroin self administration in rats responding under a continuous reinforcement schedule.…”

mentioning

confidence: 99%

Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

McMahon

Gerak

et al. 2008

Psychopharmacology

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Rationale-Opioid receptor agonists can enhance some effects of cannabinoid receptor agonists and cannabinoid receptor agonists can enhance some effects of opioid receptor agonists; however, the generality of these interactions is not established.Objective-This study examined interactions between the discriminative stimulus and antinociceptive effects of μ opioid receptor agonists and Δ 9 -tetrahydrocannabinol (THC) in rhesus monkeys.Results-Neither heroin nor morphine (i.v. or s.c.) altered the discriminative stimulus effects of THC in monkeys (n=5) discriminating 0.1 mg/kg THC i.v. In contrast, THC (s.c.) markedly attenuated the discriminative stimulus effect of morphine and heroin in non-dependent monkeys (n=4) discriminating 1.78 mg/kg morphine s.c. Doses of THC that attenuated the discriminative stimulus effects of morphine in non-dependent monkeys failed to modify the discriminative stimulus effects of morphine in morphine-dependent (5.6 mg/kg/12 hr) monkeys (n=4) discriminating 0.0178 mg/kg naltrexone s.c. THC also failed to modify the discriminative stimulus effects of naltrexone in morphine-dependent monkeys or the effects of midazolam in monkeys (n=4) discriminating 0.32 mg/kg midazolam s.c. Doses of THC (s.c.) that attenuated the discriminative stimulus effects of morphine in non-dependent monkeys enhanced the antinociceptive effects of morphine (s.c.) in non-dependent monkeys. While μ receptor agonists did not alter the discriminative stimulus effects of THC, in a context-dependent manner THC altered the effects of μ receptor agonists.Conclusion-That the same doses of THC enhance, attenuate, or do not affect morphine, depending on the condition, suggests that attenuation of morphine by THC can result from perceptual masking rather than common pharmacodynamic mechanisms or pharmacokinetic interactions. Keywordsopioid; THC; drug discrimination; rhesus monkey; perceptual masking; morphine; heroin; midazolam; naltrexone; antinociception Cannabinoid receptor agonists and μ opioid receptor agonists have some effects in common (e.g. antinociception): drugs from both classes have important therapeutic effects and some are abused (e.g., marijuana and heroin). Cannabinoid and opioid systems and drugs interact under a broad range of conditions, from cellular (Rios et al. 2006) to behavioral (e.g. Haney NIH Public AccessAuthor Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2012 October 24.Published in final edited form as:Psychopharmacology (Berl). 2008 August ; 199(2): 199-208. doi:10.1007/s00213-008-1157-0. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript2007) measures of drug action. Understanding these interactions could be especially important for developing novel medications that might comprise both cannabinoid and opioid mechanisms and for understanding the factors that contribute to polydrug abuse.Especially relevant to polydrug abuse are studies on the combined effects of opioids and cannabinoids on behavioral measures that are related to and p...

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Δ9-Tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats

Cited by 138 publications

References 34 publications

Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats

Cellular Mechanisms Underlying the Anxiolytic Effect of Low Doses of Peripheral Δ9-Tetrahydrocannabinol in Rats

Behavioral and temperature effects of delta 9-tetrahydrocannabinol in human-relevant doses in rats

Interactions between Δ9-tetrahydrocannabinol and μ opioid receptor agonists in rhesus monkeys: discrimination and antinociception

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