Psychoactive cannabinoids produce several effects on the central nervous system attributable to specific interactions with their receptors (CB). Two subtypes of CB receptors have been identified: the CB1 receptor is widely distributed in the brain and CB2 receptor is found predominantly in the spleen and haemopoietic cells. The aim of the present study was to assess the acute effects of the primary psychoactive constituent of cannabis, delta9-tetrahydrocannabinol (THC), on noradrenaline (NA) synthesis in the rat brain in vivo.

Groups of four male Sprague-Dawley rats (220-300 g) were treated with vehicle (ethanol:cremofor:water; 1:1:18; 1 ml kg^-1, I.P.) or different doses of THC (5, 10 and 20 mg kg^-1, I.P.) and animals were killed by decapitation 1 h later. All animals were injected with the inhibitor of the aromatic L-amino acid decarboxylase NSD 1015 (3-hydroxybenzyl-hydrazine HCL, 100 mg kg^-1, I.P.) 30 min before killing and the accumulation of 3,4-di-hydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a mesure of the rate of tyrosine hydroxylation. The brain was rapidly removed and different regions were dissected (a piece of brainstem containing the locus coeruleus, hippocampus, hypothalamus, parieto-occipital cortex and frontal cortex) and they were stored at -80 °C. Brain regions were homogenized and DOPA and NA were detected by HPLC with electrochemical detection. ANOVA followed by Scheffé’s test was used for statistical evaluation. This study was approved by the research and ethical review board of the Dirección General de Investigación (MCT, Madrid) and the experiments were performed according to the guidelines of the Univesity of Balearic Islands.

THC induced dose-dependent increases in DOPA accumulation in locus coeruleus (71 ± 17 %, P < 0.05), hippocampus (70 ± 11 %, P < 0.01), hypothalamus (56 ± 5 % P < 0.001) and parieto-occipital cortex (56 ± 7 %, P < 0.005). Also THC induced a dose-dependent decrease in total content of NA in hippocampus and hypothalamus (39 ± 9 %, P < 0.05) probably as a result of NA release. In contrast, no changes were observed in frontal cortex. Moreover, the acute administration of the selective CB1 agonist WIN 55,212-2 (2 mg kg^-1, I.P.) also increased DOPA accumulation and decreased NA content in hippocampus and hypothalamus.

In summary, these results indicate a stimulating effect of cannabinoids on NA synthesis and suggest an implication of CB1 cannabinoid receptor in these effects.

This work was supported by grant BFI2000-306 (MCYT, Spain). D.M. was supported by a FPI fellowship (MCYT, Spain).