ABSTRACT
In the course of our previous analyses of gustatory reward processes, we showed that, in normal or sham-lesioned rats, the preference threshold for saccharin over water was observed with a 0.3mM solution of the sweetener. The same solution was neutral for rats whose lateral hypothalamic neurones had been destroyed by ibotenic acid. Furthermore, injection of small dose of morphine (50ng) in the second gustatory relay-station, the parabrachial area, suppressed preference for the 0.3mM saccharin solution in sham-lesioned rats, while the same injection induced preference in lesioned rats. The aim of the present study was to determine if this paradoxical effect of morphine, in particular the suppressive action observed in sham-lesioned rats, could be explained by a differential activation of µ and kappa receptors located in the parabrachial area. Using the choice test between 0.3mM solution of saccharin and water, we compared the effect of intra-parabrachial injection of 50ng of morphine to those obtained with the µ agonist DAGO, the putative endogenous kappa ligand, dynorphin A(1-13) (Dyn A(1-13)) and the kappa antagonist, nor-binaltorphimine (nor-BNI). Increasing doses of each agonist and the antagonist were tested in independent groups of rats including lesioned and sham-lesioned animals. The same doses of DAGO that increased preference in sham-lesioned animals, decreased saccharin and water intakes in lesioned rats. On the contrary, Dyn A(1-13) dose-dependently decreased preference in the control rats and increased preference in lesioned animals. The effects of increasing doses of nor-BNI were more variable. To clarify the respective roles of the µ and kappa receptors, we tested the effect of two mixtures: (1) the simultaneous injection of DAGO and Dyn A(1-13) at doses ineffective when tested separately reproduced the paradoxical effect of morphine in each group of rats; (2) morphine effects were reversed when kappa receptors were blocked by a prior injection of nor-BNI. Taken together, the results suggest that: (1) in the parabrachial area of the normal rat, two opioidergic components, behaving antagonistically to each other, are implicated in the control of gustatory preference, a µ component with rewarding properties and a kappa component with aversive properties; (2) the main effect of the lateral hypothalamic lesion is to invert the properties of these two components; and (3) at least in the parabrachial area, µ and kappa receptors are functionally coupled and must be co-activated to reproduce the full effect of morphine.
ABSTRACT
The aim of the present study was to analyze the effects of morphine injected into the second relay station of the gustatory input pathways, the parabrachial area, on preference for saccharin over water. This study was carried out using both rats whose lateral hypothalamic neurons had been lesioned by ibotenic acid and sham-lesioned rats. As already shown, an 0.3 mM solution of the sweetener, which was clearly preferred over water by the sham-lesioned animals, was neutral for the lesioned rats. The injection of 50 ng of morphine into each parabrachial area transformed this neutral response of the lesioned rats to a clear preference for the sweetener, whereas the preference of sham-lesioned rats for the same solution was converted to an aversive response. Likewise, with a more palatable solution of saccharin (2.5 mM), the injection of 50 ng of morphine decreased the preference of the nonlesioned rats but increased the preference of the lesioned animals. Using the 2.5 mM solution of saccharin, the intraparabrachial injection of higher doses of morphine (100 and 500 ng) did not greatly modify the preference for the sweetener but induced a significant decrease in total fluid intake that was still observed 11 h after the injection of the opiate. These results are discussed: the morphine-induced aversion observed in the nonlesioned rats could be explained either by a specific influence on certain opioid receptors in the parabrachial area or, more probably, by the stimulation of pathways involved in taste or visceral aversive processes and relaying in the parabrachial area.(ABSTRACT TRUNCATED AT 250 WORDS)
