Inactivation of the median raphe nucleus increases intake of sucrose solutions: a microstructural analysis

Abstract

Previous studies have shown that microinjections of the GABA-A agonist muscimol into the median raphe nucleus (MR) result in large increases in the intake of solid foods. In the current study, we used microstructural techniques to characterize the effects of intra-MR muscimol injections on the consumption of either a 0.05 M or a 0.29 M sucrose solution. After injections of either saline or muscimol, animals consumed more of the 0.29 M than the 0.05 M solution, an effect which resulted primarily from increases in the initial rate of consumption with no change in the rate at which licking decayed across the test session. In contrast, intra-MR muscimol injections had little effect on the initial licking rate, but greatly increased meal duration, indicating that this treatment affected ingestion in a different way than did altering the sucrose concentration. Muscimol injections produced a significantly larger increase in the intake of the 0.29 M than of the 0.05 M solution. Intra-MR muscimol injections did not alter the within burst rate of licking, suggesting that they did not affect the functioning of the licking pattern generator. In contrast, these injections did increase the number of licks contained within "clusters," that is groups of licks separated from each other by intervals of more than 0.5 sec. These findings show that inactivation of the MR produces a powerful effect on the intake of liquid diets, and that the nature of this effect is different from that produced here by changes in sucrose concentration and from those reported after pharmacological manipulations of a number of other brain systems. We additionally discuss several theoretical issues arising in the interpretation of microstructural data. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Fig. 1

Histologically determined location of cannula tips for subjects in the current study. All cannulae tips (small dots) were located in the medial portion of the MR. Tip locations were within 0.3 mm of the coronal plane depicted in this illustration. Abbreviations: ATN=anterior tegmental nucleus, CG=central grey substance, DBC=decussation of the brachium conjunctivum, DR=dorsal raphe nucleus, IC=inferior colliculus, MLF=medial longitudinal fasciculus, ML=medial lemniscus, MR=median raphe nucleus, NRTP=nucleus reticularis tegmenti pontis, VLL=ventral nucleus of the lateral lemniscus. Dashed lines extending from the ATN to the NRTP represent the medial borders of the predorsal bundle.

Fig. 2

Effects of sucrose concentration and intra-MR muscimol injections on macrostructural aspects of feeding. The upper left panel shows effects of sucrose and muscimol on the volume of intake across the 60 min test session. The upper right panel shows effects on the total numbers of licks. The middle left panel displays mean numbers of licks needed to consume 1 ml of fluid. The middle right panel shows the mean duration of eating, i.e., the mean interval between the first and last licks made in the test session. The lower left panel shows mean rates of intake over the duration of the eating, i.e., the mean ratios of total licks to the duration of eating. The lower right panel shows the numbers of licks made in the first 9 min of the test session. See text for statistical details.

Fig. 3

Mean numbers of licks made in three min. time bins for animals injected with saline or 25 ng muscimol into the MR who were allowed to drink sucrose at concentrations of 0.5 or 0.29M.

Fig. 4

The upper two panels show examples of exponential curve fits for cumulative licking data for a typical subject in the low sucrose condition (upper left panel) and one in the high sucrose condition (upper right panel). Licking after saline injections is shown in triangles, and after muscimol injections in circles. Data were fit to the equation “cumulative licks = ab(1-e^−t/b)”. Note the difference in scales between the two figures. The large difference in overall intakes between the two animals is due primarily to the more than 5 fold increase in the “a” parameter, which reflects the initial rate of drinking, whereas the effects of muscimol were due primarily to changes in the time constant “b”. The lower two panels show mean values of the initial rate constant and the time constant after saline and muscimol injections for animals in the two sucrose conditions.

Fig. 5

Effects of sucrose concentration and muscimol injections on the size of clusters (upper left panel), interval between clusters (upper right panel), and number of clusters (lower left panel) across the 60 min test session. The lower right panel shows numbers of clusters across the first 9 min of the test. (See text for details.)

Fig. 6

The percentage of the total number of interlick intervals (ILIs) which fell between 0.25 and 0.5 sec in the interburst interval (IBI) range. The effect of muscimol was statistically significant, whereas that of sucrose concentration was not. (See text for details.)