3. Umbruch 4.4..2005 - Online Pot

192 L.A. Parker et al.
Anecdotal evidence suggests that ∆ 9 -THC alleviates ANV in chemotherapy
patients [40, 59, 60]. Although there has been considerable experimental
investigation of unconditioned vomiting in response to toxins, there have
been relatively few reports of conditioned emetic reactions elicited by
re-exposure to a toxin-paired cue (ANV). Conditioned gaping and retching
has been observed to occur in coyotes, wolves and hawks upon re-exposure
to cues previously paired with lithium-induced toxicosis [74, 75] and ferrets
have been reported to display conditional emetic reactions during exposure to
a chamber previously paired with lithium-induced toxicosis [76]. We [77]
have presented a model of ANV based on the emetic reactions of S. murinus.
Following two pairings of a novel distinctive contextual cue with the emetic
effects of an injection of lithium chloride, the context acquired the potential
to elicit gaping in the absence of the toxin. The expression of this conditioned
reaction was completely suppressed by pretreatment with ∆ 9 -THC at a dose
that did not suppress general activity. This provides the first experimental evidence
in support of anecdotal reports that ∆ 9 -THC suppresses ANV.
Conditioned gaping in rats: a model of nausea
Nausea has been reported to be the most unpleasant and distressing aspect of
chemotherapy, superceding even vomiting and retching [14]. Nausea is less
effectively reduced by the 5-HT 3 receptor antagonists than is acute vomiting
[1, 9, 10, 14, 20]. Even when the cisplatin-induced emetic response is blocked
in the ferret by administration of a 5-HT 3 receptor antagonist, c-fos activation
still occurs in the area postrema, suggesting that an action here may be responsible
for some of the other effects of cytotoxic drugs, such as nausea or
reduced food intake [12]. Grundy and colleagues [78–80] have demonstrated
that in rats the gastric afferents respond in the same manner to physical and
chemical (intragastric copper sulfate and cisplatin) stimulation that precedes
vomiting in ferrets (presumably resulting in nausea that precedes vomiting).
Furthermore, 5-HT 3 antagonists that block vomiting in ferrets also disrupt this
preceding neural afferent reaction in rats. That is, in the rat the detection mechanism
of nausea is present, but the vomiting response is absent [81].
Nauseogenic doses of cholecystokinin and lithium chloride induce specific
patterns of brainstem and forebrain c-fos expression in ferrets that are similar
to c-fos expression patterns in rats [82]. In a classic review paper, Borrison and
Wang [83] suggest that the rats’ inability to vomit can be explained as a species-adaptive
neurological deficit and that, in response to emetic stimuli, the
rat displays autonomic and behavioral signs corresponding to the presence of
nausea, called the prodromata (salivation, papillary dilation, tachypnoea and
tachycardia).
Over a number of years, our laboratory has provided considerable evidence
that conditioned nausea in rats may be displayed as a conditioned rejection
reaction [84–89] using the Taste Reactivity (TR) test [90]. When rats are intra-