Cannabinoid-induced motor incoordination through the cerebellar CB 1 receptor in mice

Cannabinoid-induced motor incoordination through the cerebellar CB 1 receptor in mice Cannabinoids are known to impair motor function in humans and laboratory animals. We have observed dose-dependent motor incoordination in mice evaluated by rotorod following direct intracerebellar (icb) microinjection of synthetic cannabinoid agonists CP55,940 (5–25 μg) and HU-210 (1.56–6.25 μg), through permanently implanted stainless steel guide cannulas. The motor incoordination was marked at 15, 35 and 55 min post-microinjection. The motor incoordination elicited by HU-210 (6.25 μg) and CP55,940 (20 μg) was significantly blocked by the CB 1 receptor-selective antagonist SR141716A (25 μg icb), indicating mediation by a cerebellar CB 1 receptor. Further direct evidence of CB 1 mediation was obtained through a CB 1 receptor antisense/mismatch oligodeoxynucleotide approach (3 μg/12 h; total of six doses). Mice treated with intracerebellar antisense had a significantly diminished motor incoordination response to intracerebellar CP55,940 15 μg compared to mice that received intracerebellar mismatch or no prior treatment. Also, the response to intracerebellar CP55,940 in the CB 1 mismatch-treated mice did not differ from the mice that received only CP55,940. A separate study using a cerebellar tissue punching technique, following intracerebellar ( 3 H)-CP55,940 microinjection, confirmed that cannabinoid drug dispersion following microinjections was exclusively confined to the cerebellum. Microinjection of CP55,940 (20 μg) into the hippocampus, an area with a large density of CB 1 receptors, did not impair motor coordination. Taken together, these results indicate that cannabinoid-induced motor impairment occurs by activation of a CB 1 receptor in the cerebellum. The participation of other brain motor areas in cannabinoid-induced motor incoordination will require future study. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmacology Biochemistry and Behavior Elsevier

Cannabinoid-induced motor incoordination through the cerebellar CB 1 receptor in mice

Loading next page...
 
/lp/elsevier/cannabinoid-induced-motor-incoordination-through-the-cerebellar-cb-1-PN4X0j7bWq
Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science Inc.
ISSN
0091-3057
eISSN
1873-5177
D.O.I.
10.1016/S0091-3057(01)00539-1
Publisher site
See Article on Publisher Site

Abstract

Cannabinoids are known to impair motor function in humans and laboratory animals. We have observed dose-dependent motor incoordination in mice evaluated by rotorod following direct intracerebellar (icb) microinjection of synthetic cannabinoid agonists CP55,940 (5–25 μg) and HU-210 (1.56–6.25 μg), through permanently implanted stainless steel guide cannulas. The motor incoordination was marked at 15, 35 and 55 min post-microinjection. The motor incoordination elicited by HU-210 (6.25 μg) and CP55,940 (20 μg) was significantly blocked by the CB 1 receptor-selective antagonist SR141716A (25 μg icb), indicating mediation by a cerebellar CB 1 receptor. Further direct evidence of CB 1 mediation was obtained through a CB 1 receptor antisense/mismatch oligodeoxynucleotide approach (3 μg/12 h; total of six doses). Mice treated with intracerebellar antisense had a significantly diminished motor incoordination response to intracerebellar CP55,940 15 μg compared to mice that received intracerebellar mismatch or no prior treatment. Also, the response to intracerebellar CP55,940 in the CB 1 mismatch-treated mice did not differ from the mice that received only CP55,940. A separate study using a cerebellar tissue punching technique, following intracerebellar ( 3 H)-CP55,940 microinjection, confirmed that cannabinoid drug dispersion following microinjections was exclusively confined to the cerebellum. Microinjection of CP55,940 (20 μg) into the hippocampus, an area with a large density of CB 1 receptors, did not impair motor coordination. Taken together, these results indicate that cannabinoid-induced motor impairment occurs by activation of a CB 1 receptor in the cerebellum. The participation of other brain motor areas in cannabinoid-induced motor incoordination will require future study.

Journal

Pharmacology Biochemistry and BehaviorElsevier

Published: May 1, 2001

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off