Place aversion induced by blockade of μ or... : Behavioural Pharmacology (original) (raw)

Place aversion induced by blockade of μ or activation of κ opioid receptors in the dorsal periaqueductal gray matter

A.B. Sante
M.J. Nobre
M.L. Brandão

Behavioural Pharmacology

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583

589

November 2000

Neural circuits in the dorsal periaqueductal grey matter (DPAG) play an important role in the integration of defensive behaviour. As considerable numbers of μ and κ opioid receptors have been found in this region, we studied the effects of morphine, [ 3 H]-[H- d -Phe-Cys-Tyr- d -Trp-Orn-Thr-Pen-Thr-NH 2 ] (CTOP), a selective peptide antagonist for μ opioid receptors, U-50488H, a specific agonist for κ opioid receptors, and nor-binaltorphimine (nor-BNI), a long-lasting selective antagonist for κ opioid receptors, injected into the DPAG of rats submitted to the corral method, a conditioned place preference test. The behavioural testing apparatus was a circular open field consisting of four uniform quadrants that were equally preferred by the rats prior to drug treatments. For conditioning, rats received drug injections on three consecutive days and were placed into their assigned quadrant. Injection of 40 nmol of morphine into the DPAG produced place aversion effects, with reduced time spent in the drug-paired quadrant on the testing day. These place aversion effects were not inhibited by previous DPAG microinjection of CTOP (1 nmol) but were significantly reduced by prior systemic injections of nor-BNI (2 mg/kg). Microinjection of CTOP alone produced a clear decrease in the time spent in the treatment quadrant, whereas nor-BNI alone did not. Similarly, microinjection into the DPAG of the κ agonist U-50488H (10 nmol) mimicked the effects of morphine, also producing place aversion for the drug-paired quadrant. These findings suggest that blockade of μ opioid receptors or activation of κ opioid receptors in the DPAG may produce conditioned place aversion.