Taste aversions conditioned with intravenous copper sulfate: attenuation by ablation of the area postrema.

Borison and Wang identified the area postrema as the locus of chemoreceptors that mediate emetic reflexes elicited by blood-borne toxins. In the present experiments we have extended a systematic investigation of the afferent pathways mediating taste aversions by examining the effects of area postrema lesions on the aversions that follow either intravenous or intragastric administration of copper sulfate. Intrajugular cannulas were implanted in rats after ablation of the area postrema (Group AP-L) and in operated controls (Group AP-C). Every third day rats were offered a saccharin solution and immediately afterward were injected intravenously with 0.05 ml isotonic CuSO4. A group of pseudo-conditioned rats (Group SAC-C) was injected with CuSO4 approximately 24 h after ingestion of saccharin. Compared to controls animals, rats with area postrema damage acquired significantly weaker aversions to saccharin when it was paired repeatedly with intravenous CuSO4. After three conditioning trials, the rats in Group AP-L that were most resistant to acquisition of a taste aversion (Group AP-L) were again offered saccharin, but ingestion in this case was followed immediately by intragastric injection of CuSO4. After a single conditioning trial rats in Group AP-L demonstrated a robust aversion. The results are discussed in terms of the parallels in afferent systems between emetic physiology and some instances of taste aversion conditioning.

Vagotomy facilitates extinction of conditioned taste aversions in rats.

Results from three experiments indicate that severing the subdiaphragmatic vagus in rats increased the rate of extinction of learned taste aversions. In Experiment 1, although vagotomized rats acquired a saccharin aversion equivalent to that of controls when the illness-inducing agent was the blood-borne toxin apomorphine, vagotomized rats tended to consume more saccharin than controls during repeated extinction tests. In Experiment 2, vagotomy disrupted retention and increased extinction of a preoperatively acquired saccharin aversion. Disruptions were found when the taste aversion was induced by copper sulfate, a local gastric irritant (Experiment 2A), or apomorphine, a systemic toxin (Experiment 2B); in each experiment vagotomized rats consumed more saccharin than controls on the first retention test and extinguished the prior to surgery. Experiment 3 demonstrated that vagotomy did not affect retention or extinction of a shock-induced conditioned emotional response (lick to suppression) to noise. It is concluded that integrity of the vagus is not necessary for acquisition of a learned taste aversion when a blood-borne toxin is used as the ill-inducing agent. However, the vagus apparently mediates an integral portion of the conditioned response following taste-illness acquisition regardless of whether the illness agent is a local gastric irritant or a systemic toxin.

Cells of origin of motor axons in the subdiaphragmatic vagus of the rat.

The central cell groups that give rise to the motor axons that travel in the subdiaphragmatic vagus were re-examined in the rat by transecting the dorsal or ventral vagus near the stomach and incubating the nerve stump in crystalline horseradish peroxidase (HRP). An exceedingly large percentage of cells was labeled throughout the dorsal motor nucleus of the vagus (mX), with labeled cells extending even beyond the rostro-caudal limits of the nucleus usually assigned on the basis of cytoarchitecture alone. Different patterns of cell-labeling could be correlated with one or the other of the two vagal branches. Incubation of the ventral branch labeled cells only in the left mX, while incubation of the dorsal branch labeled cells on both sides, although more extensively on the right. HRP-positive somata were also observed bilaterally in the nucleus ambiguus (NA) after incubation of either branch of the subdiaphragmatic vagus; this finding is in contrast to previous accounts in which motor fibers from NA were considered to project only to cervical and thoracic structures. These results suggest that mX and NA are responsible for a substantial component of abdominal innervation in the rat.

The attenuation of a specific cue-to-consequence association by antiemetic agents.

Previous research has been shown that rats develop a conditioned taste aversion after a single pairing of a distinct taste and subsequent toxicosis. The experiments reported here test the hypothesis that the expression of a taste aversion may reflect classically conditioned nausea mediated by activation of brainstem emetic centers by taste stimuli. Rats were allowed to drink a saccharin solution (1 g/l) and 10 min later were intubated with LiCl (180 mg/kg) to produce nausea. When control rats were posttested for saccharin preference they consumed less than 50% of their pretest intake. Experimental rats were injected with one of four pharmacologically distinct antiemetic drugs 30 min prior to their posttest with saccharin. Each drug significantly attenuated the aversion to saccharin at one dose level. The antiemetic drugs we used were scopolamine HBr, cyclizine, prochlorperazine dimaleate, and trimethobenzamide. These drugs had no effect on the conditioned fear of a noise that signaled foot shock or on a natural aversion to a bitter fluid (quinine monohydrochloride, 100 mg/l). Our data suggest that pharmacological suppression of the neural mechanisms of emesis selectively disrupts conditioned taste aversions, and that moderate dose levels are critical for obtaining this effect.