Delta 9-tetrahydrocannabinol-induced catalepsy-like immobilization is mediated by decreased 5-HT neurotransmission in the nucleus accumbens due to the action of glutamate-containing neurons.
K Sano, K Mishima, E Koushi, K Orito, Nobuaki Egashira, K Irie, K Takasaki, Shutaro Katsurabayashi, K Iwasaki, N Uchida, T Egawa, Y Kitamura, R Nishimura, Michihiro Fujiwara
Neuroscience January 24, 2008 DOI: 10.1016/j.neuroscience.2007.10.026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | THC SR141716 haloperidol 5-hydroxy-L-tryptophan (5-HTP) 5-methoxy-N N-dimethyltryptamine (5-MeODMT) MK-801 amantadine |
| Topics | Cannabis Serotonin |
| Key findings | THC dose-dependently induced catalepsy-like immobilization in rats that was mechanistically distinct from haloperidol-induced catalepsy, being reversible by sensory stimuli, blocked by the CB1 antagonist SR141716, and dependent on the nucleus accumbens and central amygdala. THC decreased serotonin and glutamate release in the nucleus accumbens, and the authors propose the immobilization is mediated by reduced serotonergic neurotransmission via glutamate-containing neurons. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Δ(9)-THC and WIN55,212-2 affect brain tissue levels of excitatory amino acids in a phenotype-, compound-, dose-, and region-specific manner. Behavioural Brain Research October 10, 2011
- Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats. Pharmacology, Biochemistry, and Behavior August 2009
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