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.
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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)