Delta(9)-tetrahydrocannabinol (
THC) has been reported to induce
catalepsy-like immobilization, but the mechanism underlying this effect remains unclear. In the present study, in order to fully understand the neural circuits involved, we determined the brain sites involved in the immobilization effect in rats.
THC dose-dependently induced
catalepsy-like immobilization.
THC-induced
catalepsy-like immobilization is mechanistically different from that induced by
haloperidol (HPD), because unlike HPD-induced
catalepsy, animals with
THC-induced
catalepsy became normal again following sound and air-puff stimuli.
THC-induced
catalepsy was reversed by
SR141716, a selective
cannabinoid CB(1) receptor antagonist. Moreover,
THC-induced
catalepsy was abolished by lesions in the nucleus accumbens (NAc) and central amygdala (ACE) regions. On the other hand, HPD-induced
catalepsy was suppressed by lesions in the caudate putamen (CP), substantia nigra (SN), globus pallidus (GP), ACE and lateral hypothalamus (LH) regions. Bilateral microinjection of
THC into the NAc region induced
catalepsy-like immobilization. This
THC-induced
catalepsy was inhibited by
serotonergic drugs such as 5-hydroxy-L-tryptophan (5-HTP), a
5-HT precursor, and
5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a
5-HT receptor agonist, as well as by anti-glutamatergic drugs such as
MK-801 and
amantadine, an
N-methyl-d-aspartate (
NMDA) receptor antagonist.
THC significantly decreased
5-HT and
glutamate release in the NAc, as shown by in vivo microdialysis.
SR141716 reversed and
MK-801 inhibited this decrease in
5-HT and
glutamate release. These findings suggest that the
THC-induced
catalepsy is mechanistically different from HPD-induced
catalepsy and that the
catalepsy-like immobilization induced by
THC is mediated by decreased
5-HT neurotransmission in the nucleus accumbens due to the action of
glutamate-containing neurons.