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Giuliani 2000

Giuliani 2000

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Published by: Matias Ceballos Guzman on Dec 09, 2010
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Pharmacological Research, Vol. 41, No. 1, 2000 
Article No. phrs.1999.0560, available online at http:
rr 
www.idealibrary.com on
THE CANNABINOID AGONIST HU 210 MODIFIES RAT BEHAVIOURALRESPONSES TO NOVELTY AND STRESS
D. GIULIANI, F. FERRARI
U
and A. OTTANI
Department of Biomedical Sciences, Di 
¨
ision of Pharmacology, Uni 
¨
ersity of Modena,
¨
ia G. Campi 287, I-41100, Modena, Italy 
Accepted 7 June 1999
Experiments were performed on groups of rats after acute and sub-chronic treatment
Ž
oncedaily for 9 days
.
with the cannabinoid agonist HU 210
Ž
25 100 g kg
y
1
, i.p.
.
as well as 24 hand 7 days after the last drug injection. The animals underwent three behavioural tests innovel environments. In the observation cages
Ž
Test 1
.
, rat locomotor activity was found tobe dose-dependently reduced after acute and sub-chronic treatment at all doses andvirtually unchanged during abstinence; grooming was potently inhibited by acute treatmentbut potentiated by the sub-chronic one at doses of 50 and 100 g kg
y
1
, the effect of thehigher dose persisting after 24 h and 7 days abstinence. Vocalization in animals in responseto a tactile stimulus was highest after HU 210 at 100 g kg
y
1
in all experimental modesexcept after 7 days abstinence. In the X-maze
Ž
Test 2
.
, sub-chronic HU 210 dose-dependently enhanced rat natural aversion for open arms, and this behaviour persistedduring abstinence after the highest dose. Grooming in the X-maze was completely absent inrats acutely injected with HU 210 but potentiated in those sub-chronically treated or abstinent. In the swimming test
Ž
Test 3
.
rats sub-chronically treated at 50 and 100 pg kg
y
1
displayed relevant wall-hugging and the same occurred 24 h after last injection. On thewhole, our results are indicative of an anxiogenic-like effect of sub-chronic HU 210 at highdoses and reflect the persistence of enhanced emotional response to novel environmentswhen the treatment is discontinued.
2000 Academic PressEY WORDS: cannabinoids, HU 210, anxiety-like state, rat.
INTRODUCTIONIt is well established that the psychotropic effects of 
9
-tetrahydrocannabinol
Ž
9
-THC
.
, the major activecomponent of marijuana
w
1
x
, are linked to changes inthe activity of central neurotransmitter systems
w
2 4
x
.The discovery of specific central cannabinoid bind-ing sites
Ž
CB1
.w
5 8
x
which seem to be primarilyinvolved in many of the behavioural and physiologi-cal alterations produced in humans and animals by
9
-THC
w
9 13
x
, has led to the synthesis of a number of new cannabinoids
w
10, 12
x
. Of those, HU 210 hasdemonstrated a high degree of correlation betweenits producing ability to
in
bind
¨
¨
o
to effects CB
1
receptors
w
13 and its efficacy in16
x
. Several clinical

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