Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats
Finn, David P.
Jhaveri, Maulik D.
Beckett, Simon Richard Graham
Roe, Clare H.
Kendall, David A.
Marsden, Charles Alexander
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Finn, D. P., Jhaveri, M. D., Beckett, S. R. G., Roe, C. H., Kendall, D. A., Marsden, C. A., & Chapman, V. (2003). Effects of direct periaqueductal grey administration of a cannabinoid receptor agonist on nociceptive and aversive responses in rats. Neuropharmacology, 45(5), 594-604. doi:https://doi.org/10.1016/S0028-3908(03)00235-1
The analgesic potential of cannabinoids may be hampered by their ability to produce aversive emotion when administered systemically. We investigated the hypothesis that the midbrain periaqueductal grey (PAG) is a common substrate mediating the anti-nociceptive and potential aversive effects of cannabinoids. The rat formalin test was used to model nociceptive behaviour. Intra-PAG microinjection of the excitatory amino acid d,l-homocysteic acid (DLH) was used to induce an aversive, panic-like reaction characteristic of the defensive “fight or flight” response. Administration of the cannabinoid receptor agonist HU210 (5 μg/rat) into the dorsal PAG significantly reduced the second phase of formalin-evoked nociceptive behaviour, an effect which was blocked by co-administration of the CB1 receptor antagonist SR141716A (50 μg/rat). This anti-nociceptive effect was accompanied by an HU210-induced attenuation of the formalin-evoked increase in Fos protein expression in the caudal lateral PAG. Intra-dorsal PAG administration of HU210 (0.1, 1 or 5 μg/rat) significantly reduced the aversive DLH-induced explosive locomotor response. The anti-nociceptive effect of HU210 is likely to result from activation of the descending inhibitory pain pathway. Mechanisms mediating the anti-aversive effects of cannabinoids in the PAG remain to be elucidated. These data implicate a role for the PAG in both cannabinoid-mediated anti-nociceptive and anti-aversive responses.