Differential role of the nitric oxide pathway on delta(9)-THC-induced central nervous system effects in the mouse.
S C Azad, Giovanni Marsicano, I Eberlein, J Putzke, W Zieglgänsberger, R Spanagel, Beat Lutz
European Journal of Neuroscience February 2001 DOI: 10.1046/j.1460-9568.2001.01431.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Neuronal nitric oxide synthase (nNOS) knockout mice and wild-type controls |
| Intervention | Delta(9)-tetrahydrocannabinol |
| Dose | 10 mg/kg |
| Measures | hot plate latency, body temperature, locomotor activity, in situ hybridization |
| Topics | Cannabis |
| Key findings | Delta(9)-THC-induced antinociception was similar in nNOS knockout and wild-type mice, but hypothermia and reduced locomotion occurred only in wild-type mice. CB1 mRNA levels were lower in the ventromedial hypothalamus and caudate putamen of knockouts, and nNOS and CB1 were coexpressed in these regions. |
Abstract
This study investigated whether the nitric oxide pathway was involved in the central effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of cannabis sativa. Body temperature, nociception and locomotion were measured in neuronal nitric oxide synthase (nNOS) knock-out (KO) mice and wild-type (WT) controls after intraperitoneal application of Delta(9)-THC. These Delta(9)-THC-induced effects are known to be mediated through the brain-type cannabinoid receptor 1 (CB1). Therefore, in situ hybridization (ISH) experiments were performed in the adult murine brain to determine possible changes in CB1 mRNA levels in nNOS-KO, compared with WT mice, and to reveal brain areas where CB1 and nNOS were coexpressed in the same neurons. We found that an intraperitoneal injection of 10 mg/kg Delta(9)-THC led to the same increase in the hot plate latencies in both genotypes, suggesting that Delta(9)-THC-mediated antinociception does not involve nNOS. In contrast, a significant Delta(9)-THC-induced decrease of body temperature and locomotor activity was only observed in WT, but not in nNOS-KO mice. ISH revealed significantly lower levels of CB1 mRNA in the ventromedial hypothalamus (VMH) and the caudate putamen (Cpu) of the nNOS-KO animals, compared with WT mice. Both areas are known to be among the regions involved in cannabinoid-induced thermoregulation and decrease of locomotion. A numerical evaluation of nNOS/CB1 coexpression showed that approximately half of the nNOS-positive cells in the dorsolateral Cpu also express low levels of CB1. ISH of adjacent serial sections with CB1 and nNOS, revealed expression of both transcripts in VMH, suggesting that numerous nNOS-positive cells of VMH coexpress CB1. Our findings indicate that the nitric oxide pathway is involved in some, but not all of the central effects of Delta(9)-THC.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
Cites 3
- The effects of cannabinoids on the brain. Progress in Neurobiology July 1999
- Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice. Science January 15, 1999
- The functional neuroanatomy of brain cannabinoid receptors. Neurobiology of Disease December 1998