The endocannabinoid
system in the basal ganglia and in the
mesolimbic reward system: implications for
neurological and psychiatric
disorders
van der Stelt M, Di Marzo V
Endocannabinoid Research
Group, Istituto Chimica Biomolecolare, Consiglio
Nazionale delle Ricerche, Pozzuoli,
Italy.
To date, N-arachidonoylethanolamine
(anandamide) and 2-arachidonoylglycerol are the
best studied endocannabinoids and are thought to
act as retrograde messengers in the central
nervous system (CNS). By activating presynaptic
cannabinoid CB1 receptors, they can reduce
glutamate release in dorsal and ventral striatum
(nucleus accumbens) and alter synaptic
plasticity, thereby modulating neurotransmission
in the basal ganglia and in the mesolimbic
reward system.
In this review, we will focus on the role of
the endocannabinoid system within these neuronal
pathways and describe its effect on dopaminergic
transmission and vice versa. The endocannabinoid
system is unlikely to directly affect dopamine
release, but can modify dopamine transmission
trough trans-synaptic mechanisms, involving
gamma-aminobutyric acid (GABA)-ergic and
glutamatergic synapses, as well as by converging
signal transduction cascades of the cannabinoid
and dopamine receptors. The dopamine and
endocannabinoid systems exert a mutual control
on each other.
Cannabinergic signalling may lead to release
of dopamine, which can act via dopamine D1-like
receptors as a negative feedback mechanism to
counteract the effects of activation of the
cannabinoid CB1 receptor. On the other hand,
dopaminergic signalling via dopamine D2-like
receptors may lead to up-regulation of
cannabinergic signalling, which is likely to
represent a negative feedback on dopaminergic
signalling.
The consequences of these interactions
become evident in pathological conditions in
which one of the two systems is likely to be
malfunctioning. We will discuss neurological and
psychiatric disorders such as Parkinson's and
Huntington's disease, drug addiction and
schizophrenia. Furthermore, the possible role of
the endocannabinoid system in disorders not
necessarily depending on the dopaminergic
system, such as eating disorders and anxiety,
will be described.
