Effects of intra-basolateral amygdala administration of rimonabant on nociceptive behaviour and neuronal activity in the presence or absence of contextual fear.
The basolateral amygdala (BLA) contains a high density of cannabinoid CB1 receptors and is critically involved in pain and fear-related behaviour. We investigated the effects of bilateral intra-BLA administration of the CB1 receptor antagonist/inverse agonist, rimonabant, on formalin-evoked nociceptive behaviour, fear-conditioned behaviour including analgesia, and associated brain regional alterations in Fos expression in rats. Intra-BLA administration of rimonabant significantly reduced formalin-evoked nociceptive behaviour in the absence, but not presence, of conditioned fear. Rimonabant attenuated a formalin-evoked reduction in freezing while emitting 22 kHz ultrasonic vocalisation in the early part of the fear expression trial. Formalin-evoked nociceptive behaviour was associated with increased Fos immunoreactivity (FI) in the CA2/3 region of the hippocampus and rostral ventromedial medulla, effects attenuated by intra-BLA rimonabant. Formalin also decreased FI in the cingulate cortex, an effect which was not observed in fear-conditioned rats. Contextually-induced fear was associated with increased FI in the dorsal caudal periaqueductal grey in the absence, but not presence, of formalin-evoked nociceptive tone. In conclusion, bilateral intra-BLA administration of rimonabant reduces nociceptive behaviour in a model of tonic, persistent inflammatory pain, an effect associated with reduced activation of neurons in the CA2/3 hippocampus and rostral ventromedial medulla. The data also provide evidence for differential pain- and fear-related brain regional activity in the presence or absence of contextually-induced aversion and nociceptive tone.
Roche
Michelle
M
Department of Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Centre for Pain Research, National University of Ireland, Galway, Ireland.
Johnston
Patrick
P
Mhuircheartaigh
Orla Ní
ON
Olango
Weredeselam M
WM
Mackie
Kenneth
K
Finn
David P
DP
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D063387:Cannabinoid Receptor Antagonists; D002408:Catheters, Indwelling; D002452:Cell Count; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005557:Formaldehyde; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D043882:Receptors, Cannabinoid / Q000378:metabolism; D000077285:Rimonabant
D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D005557:Formaldehyde; D000077285:Rimonabant