CB1 cannabinoid receptor agonists increase
intracranial self-stimulation thresholds in the rat

Vlachou S, Nomikos GG, Panagis G.
Laboratory of Behavioral Neuroscience,
Department of Psychology,
School of Social Sciences, University of Crete,
74100 Rethymnon, Crete, Greece.
Psychopharmacology (Berl). 2005 May;179(2):498-508


RATIONALE: Addictive drugs have a number of commonalities in animal behavioral models. They lower intracranial self-stimulation (ICSS) thresholds, support self-administration, and produce conditioned place preference (CPP). However, cannabinoids appear atypical as drugs of abuse, since there are controversial data in the literature concerning their reinforcing properties. OBJECTIVES: The aim of the present study was to examine the effects of cannabinoids on brain reward using the rate-frequency curve shift paradigm of ICSS. METHODS: Male Sprague-Dawley rats were implanted with electrodes into the medial forebrain bundle (MFB). Rate-frequency functions were determined by logarithmically decreasing the number of cathodal pulses in a stimulation train from a value that sustained maximal responding to one that did not sustain responding. After brain stimulation reward thresholds stabilized rats received intraperitoneal (IP) injections of the potent CB1 receptor agonists WIN 55,212-2 (graded doses 0.1, 0.3, 1 and 3 mg/kg), CP 55,940 (graded doses 10, 30, 56 and 100 microg/kg), or HU-210 (graded doses 10, 30, 100 microg/kg). RESULTS: With the exception of the highest dose of all cannabinoid agonists tested, which significantly increased the threshold frequency required for MFB ICSS, all other doses of the tested drugs did not affect ICSS thresholds. The CB1 receptor antagonist SR141716A reversed the actions of WIN 55,212-2 and CP 55,940, but not HU-210. However, the selective CB1 cannabinoid receptor antagonist AM 251 counteracted the effect of HU-210. Both CB1 receptor antagonists, at the doses used in the present study, did not affect reward thresholds by themselves. CONCLUSIONS: The present results indicate that cannabinoid agonists do not exhibit reinforcing properties in the ICSS paradigm, but rather have an inhibitory influence on reward mechanisms. The results suggest that the anhedonic effects of cannabinoids are probably mediated by cannabinoid CB1 receptors.

Hemp oil
Swiss hemp
Hemp seeds
Tolerant mice
Just say know
Cannabis: effects
Forgetful rodents
Stoned as a newt?
Stoned chocaholics?
The nectar of delight
Charas versus bhang
Rodent cannabis abuse
Cannabinoid receptor subtypes
Cannabinoids and the zebra finch
Cannabinoid C1 receptor antagonists

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15


Future Opioids
BLTC Research
Utopian Surgery?
The Hedonistic Imperative
Ecstasy: Utopian Pharmacology
When Is It Best To Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family