Cannabinoid and dopamine interaction in rodent brain: effects on locomotor activity

Meschler, Justin P.; Conley, Thomas J; Howlett, Allyn C.

doi:10.1016/s0091-3057(00)00390-7

Cited by 44 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both CB1 and D2 receptors couple to G i-o proteins and inhibit adenylyl-cyclase, whereas their costimulation results in G s protein-dependent activation of adenylylcyclase (44,45). Moreover, CB1 receptor agonists and antagonists counteract and potentiate, respectively, D2 receptor agonist effects (46)(47)(48)(49), although D2 and CB1 receptor interactions might differ between rodents and primates (50,51). It is therefore possible that in marijuana abusers, chronic CB1 receptor stimulation prevented the striatal D2/D3 receptor down-regulation observed with repeated drug use (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Volkow

Wang

Telang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

195

147

View full text Add to dashboard Cite

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged 48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain DA responses (measured with PET and [ 11 C]raclopride) to MP between controls and marijuana abusers. Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioral ("self-reports" for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [ 11 C]raclopride, although normal reductions in striatal nondisplaceable binding potential (BP ND )] responses to MP. In ventral striatum (key brain reward region), MP-induced reductions in DVs and BP ND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving. The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.nucleus accumbens | amotivation | cannabinoid 1 receptors | brain imaging | midbrain D espite the high prevalence of marijuana consumption, the effects of marijuana abuse in the human brain are not well understood. Marijuana, like other drugs of abuse, stimulates brain dopamine (DA) signaling in the nucleus accumbens (1, 2), which is a mechanism believed to underlie the rewarding effects of drugs (3-5) and to trigger the neuroadaptations that result in addiction (reviewed in ref. 6). Indeed, in humans, imaging studies have shown that drugs of abuse increase DA release in striatum (including the nucleus accumbens), and these increases have been associated with the subjective experience of reward (7-9). However, for marijuana, the results have been inconsistent: One study reported striatal DA increases during intoxication (10); two studies showed no effects (11, 12); and one study reported DA increases in individuals with a psychotic disorder and in their relatives, but not in controls (13). Imaging studies of the brain DA system in marijuana abusers have also shown different findings from those reported for other types of substance abusers. Specifically, substance abusers (cocaine, methamphetamine, alcohol, heroin, and nicotine), but not marijuana abusers (14-16), show reduced baseline availability ...

show abstract

Section: Discussionmentioning

confidence: 99%

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Volkow

Wang

Telang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

195

147

View full text Add to dashboard Cite

show abstract

“…For example, concomitant activation of DA D2-like receptors by endogenous DA has been found to play a role in the THCinduced memory impairment and reduction of extracellular acetylcholine concentration in the hippocampus (Nava et al, 2000), while D2, but not D1 receptor agonists, potentiate cannabinoid-induced sedation in non-human primates (Meschler et al, 2000). In addition, the alteration in Fos expression that follows the blockade of CB1 receptors has been found to occur via reduced D2-like receptor-mediated function (Alonso et al, 1999).…”

Section: Da-cannabinoid Interaction and The Effects Of Cocaine In Thementioning

confidence: 99%

A Critical Interaction between Dopamine D2 Receptors and Endocannabinoids Mediates the Effects of Cocaine on Striatal GABAergic Transmission

Centonze

Battista

Rossi

et al. 2004

Neuropsychopharmacol

136

112

View full text Add to dashboard Cite

Compelling evidence indicates that endocannabinoids are implicated in drug addiction. In the present study, we have addressed the interaction between cocaine and endocannabinoid system by means of neurochemical and neurophysiological experiments in rat brain slices. Using gas chromatography-electron impact mass spectrometry, we have found that cocaine increased the levels of the endocannabinoid anandamide in the striatum, a brain area primarily involved in the compulsive drug-seeking and drug-taking behaviors typical of addiction. This effect was attenuated by pharmacological inhibition of D2-like receptors but not D1-like receptors, and it was mimicked by D2-like but not D1-like receptor stimulation. The cocaine-induced increase in anandamide concentrations was attributable to both stimulation of its synthesis and inhibition of its degradation, as suggested by the ability of cocaine and quinpirole, a D2-like receptor agonist, to enhance the activity of NAPE-phospholipase D and to inhibit fatty acid amide hydrolase. By means of electrophysiological recordings from single striatal neurons, we have then observed that the ability of cocaine to inhibit, via D2-like receptors, GABA transmission was partially prevented following blockade of cannabinoid receptors, suggesting that endocannabinoids may act as downstream effectors in the action of cocaine in the striatum. Understanding the molecular and physiological effects of drugs of abuse in the brain is essential for the development of effective strategies against addiction.

show abstract

“…It is interesting that there is a significant difference between 1 and 10 ng/rat test groups however in comparison of 10 and 100 ng/rat test groups catalepsy time has increased but there is not significant difference between them unless at 105 and 120 min after drug administration. Beside the present study have been reported that catalepsy is symmetrical to cannabinoid receptor agonist dose (Brotchie, 2003;Meschler et al, 2000;Ja¨rbe et al, 2002;Walton et al, 1938;Dewey, 1986) however Sulcova et al (1998) has demonstrated that anandamide, an endogenous cannabinoid receptor agonist, has biphasic effect on catalepsy, first anandamide reduces catalepsy and in higher doses it causes catalepsy increasment. Also Souilhac et al (1995) has reported that unilateral injection of a cannabinoid CB 1 agonist in mice leads to contralateral turning behavior.…”

Section: Figurementioning

confidence: 45%

Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity of parkinsonian rats induced by reserpine

Moghaddam

Khodayar

Zarei

et al. 2010

Saudi Pharmaceutical Journal

View full text Add to dashboard Cite

It has been observed cannabinoid CB1 receptor signalling and the levels of endocannabinoid ligands significantly increased in the basal ganglia and cerebrospinal fluids of Parkinson's disease (PD) patients. These evidences suggest that the blocking of cannabinoid CB1 receptors might be beneficial to improve movement disorders as a sign of PD. In this study, a dose-response study of the effects of intrastriatal injection of a cannabinoid CB1 receptor antagonist, AM251 and agonist, ACPA, on movement activity was performed by measuring the catalepsy of reserpinized and non-PD (normal) rats with bar test. Also the effect of co-administration the most effective dose of AM251 and several doses of ACPA were assessed. AM251 decreases the reserpine induced catalepsy in dose dependent manner and ACPA causes catalepsy in normal rats in dose dependant manner as well. AM251 significantly reverse the cataleptic effect in all three groups (1, 10, 100 ng/rat) that received ACPA. These results support this theory that cannabinoid CB1 receptor antagonists might be useful to alleviate movement disorder in PD. Also continuance of ACPA induced catalepsy in rats after AM251 injection can indicate that other neurotransmitters or receptors interfere in ACPA induced catalepsy. Based on the present finding there is an incomplete overlapping between cannabinoid CB1 receptor agonist and antagonist effects.

show abstract

Cannabinoid and dopamine interaction in rodent brain: effects on locomotor activity

Cited by 44 publications

References 25 publications

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

Decreased dopamine brain reactivity in marijuana abusers is associated with negative emotionality and addiction severity

A Critical Interaction between Dopamine D2 Receptors and Endocannabinoids Mediates the Effects of Cocaine on Striatal GABAergic Transmission

Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity of parkinsonian rats induced by reserpine

Contact Info

Product

Resources

About