Decreased Spontaneous Eye Blink Rates in Chronic Cannabis Users: Evidence for Striatal Cannabinoid-Dopamine Interactions

PLOS ONE, Nov 2011

Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR), a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0026662&type=printable

Decreased Spontaneous Eye Blink Rates in Chronic Cannabis Users: Evidence for Striatal Cannabinoid-Dopamine Interactions

Hommel B (2011) Decreased Spontaneous Eye Blink Rates in Chronic Cannabis Users: Evidence for Striatal Cannabinoid- Dopamine Interactions. PLoS ONE 6(11): e26662. doi:10.1371/journal.pone.0026662 Decreased Spontaneous Eye Blink Rates in Chronic Cannabis Users: Evidence for Striatal Cannabinoid- Dopamine Interactions Mikael A. Kowal 0 Lorenza S. Colzato 0 Bernhard Hommel 0 Antonio Verdejo Garca, University of Granada, Spain 0 Cognitive Psychology Unit and Leiden Institute for Brain and Cognition, Leiden University , Leiden , The Netherlands Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR), a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history. - Cannabis (Cannabis sativa) is the most widely used illicit drug in Europe and the US. Its recreational use dates back to over 2000 years B.C. The active compounds in cannabis are called exogenous cannabinoids, with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) being responsible for most of the drugs psychoactive effects [1]. Current research indicates that THC, as a cannabinoid CB1 receptor agonist, indirectly affects dopaminergic functioning. Stimulation of the cannabinoid receptor type 1 (CB1) results in the release of dopamine (DA) [2]a neurotransmitter involved in the control of goal-directed behavior, reward learning, reinforcement, and addiction [3]. However, CB1 receptors are not present at dopaminergic neurons. Instead, they are located in Gamma Amino Butyric Acid (GABA) and glutamatergic terminals which, in turn, influence DA/D1 and DA/D2 neurons by controlling DA inhibition. In other words, CB1 receptors contribute to the release of DA by inhibiting DA inhibitors. Interestingly, the highest concentrations of CB1 receptors in the brain can be observed at the same areas where dopaminergic neurons are present [3]. Crucial regions in this regard seem to be the basal ganglia and, more specifically, the striatum, in which endogenous cannabinoids modulate the firing of DA neurons. This occurs through postsynaptic interactions between cannabinoids and DA at the level of G-protein/adenylyl cyclase signal transduction [4]. As a consequence, it makes sense to assume that any effect of THC on DA transmission is the product of an indirect process. This is different from the impact of other often abused drugs, like amphetamine or cocaine, which seems to act directly on DA neurons (for a discussion, see [5]). Hitherto, two studies using Positron Emission Tomography have looked into the acute effect of THC on striatal DA transmission with however inconsistent results: one study reported a THCinduced increase in striatal DA level [6] while another found no effect [7]. Things are even less clear with regard to chronic effects of long-term exposure to THC, on which no data are available. This is particularly unfortunate in view of Kueppers et al. [8] suggestion that repeated THC administration may create a dopaminergic imbalance in the brain by increasing striatal DA levels but lowering DA levels in prefrontal cortex. As a possible consequence of this imbalance, chronic THC exposure has been assumed to induce psychotic symptoms in users [8]. However, a problem with this assumption is that it is not based on any evidence regarding chronic effects of THC on striatal DA transmission but on only one finding regarding the acute effects [6]. Therefore, it is not clear whether THC actually induces long-term dopaminergic imbalances. To address this issue, the present study aimed at investigating the effect of long-term exposure to cannabis on striatal DA transmission. In the case of chronic effects, it is difficult to differentiate between the specific psychoactive plant components which caused the potential impairments. Consequently, we use the more generic term cannabis in the present study, even though the available data suggest that the observed effects are mainly due to the impact of THC. For one, from the two main studied psychoactive compounds of cannabis, only THC acts as a CB1 receptor agonist, while CBD functions as an antagonist. For another, CBD is suspected to red (...truncated)


This is a preview of a remote PDF: http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0026662&type=printable

Mikael A. Kowal, Lorenza S. Colzato, Bernhard Hommel. Decreased Spontaneous Eye Blink Rates in Chronic Cannabis Users: Evidence for Striatal Cannabinoid-Dopamine Interactions, PLOS ONE, 2011, Volume 6, Issue 11, DOI: 10.1371/journal.pone.0026662