Location preference and flavor aversion reinforced by amphetamine in rats

Abstract

To associate the identical drug state with both a loeation and a flavor, rats were given intraperitoneal amphetamine injeetions and then eonfined for 20 min in one side of a shuttlebox with aecess to a flavored solution; on control trials without injections, they were confined for 20 min in the opposite side with a different flavor. In the first experiment, the rats were plaeed in the shuttlebox immediately after injections; in the second experiment, they were placed in the shuttlebox 20 min after injections. Subsequent free-choice tests in both experiments revealed an increased choice of the side of the shuttlebox associated with amphetamine but also an aversion to the flavored solution associated with the drug.In attempts to eharaeterize the reinforeing properties of abused drugs, a paradox has arisen. Cappell and l..e Blane (1973) found aversive taste eonditioning by intraperitoneal amphetamine within the range of doses which Pickens and Harris (1968) found rats would selfinjeet intravenously. Thus, a single pharmaeologieal stimulus may aet as both a positive and a negative reinforeer depending on the associated stimuli and responses.Wise, Yokel, and deWit (1976) pointed out, however, that these seemingly paradoxical effeets eould be explained by differenees in proeedural variables such as route of drug administration, extent of drug habituation, and delay of reinforeement. Wise et al. therefore attempted to eontrol for these faetors in demonstrating positive and negative reinforeement by intravenous amphetamine and apomorphine. Their first experiment circumvented habituation diffieulties by giving rats that had previously shown amphetamine self-administration a IO-min exposure to saccharin followed by an amphetamine injection. A subsequent test indicated moderate suppression of saccharin drinking. However, as the report aeknowledges, this does "not ... establish that a particular drug injection can be both reinforcing and aversive" (p. 1273). The difficulty is that positive reinforcement was demonstrated by self-adrninistered amphetamine immediately following leverpressing, while negative reinforcement was demonstrated by a single, experimenter-administered amphetamine injection given only after a IO-min drinking period. In the second experiment by Wise et al., rats previously trained to selfadminister amphetamine were given aceess to saccharin followed immediately by an apomorphine self-injection session. Some of the rats continued to leverpress for apomorphine, yet subsequently showed an aversion to the saccharin. As Wise et al. mentioned, however, there were still difficulties in this proeedure, including the difference in the delay of reinforcement for leverpressing and saccharin-drinking, as weIl as the possible ambiguity created by first training the rats to self-administer amphetamine and then suddenly switching to apomorphine.The present experiments avoided some of these problems by associating the same injections with a compound stimulus consisting of a distinctive flavor and a distinctive loeation...

Reward comparison: the Achilles’ heel and hope for addiction

“…Even so, it was viewed as highly paradoxical that such drugs, drugs that were readily selfadministered by rats and man [27], also evidenced aversive properties in the CTA paradigm. Indeed, in three key experiments, avoidance of the taste cue was found to be accompanied, in the exact same study, by faster running for the drug [28], more time spent in the drug-paired compartment in a conditioned place preference task [29], and avid self-administration of the drug [24]. Since this time, additional evidence has been generated to show that addictive agents have aversive properties [25, 30 , 31 ] and the aversive response to the taste cue following tastedrug pairings has been attributed to a range of factors including stimulus novelty, drug shyness (i.e., fear of novel drug or drug-induced state), fear [32], and positive conditioned suppression (i.e., where responding is suppressed by stimuli that precede the response-independent presentation of shock or food, for example) [33][34][35][36].…”

Interstimulus interval determines whether ethanol produces conditioned place preference or aversion in mice

“…In support ofthis suggestion, one study with morphine has shown that simultaneous conditioning produces a conditioned taste preference, whereas standard trace delay conditioning produces conditioned taste aversion (Lett & Grant, 1989). However, in other studies involving either simultaneous or short backward intervals with amphetamine, taste aversion was produced even though the same drug injection conditioned preference to exteroceptive stimuli presented together with the taste CS (Reicher & Holman, 1977). Thus, it does not appear that the place preference-taste aversion paradox can be explained entirely in terms ofISI differences.…”

“…Specifically, many reports show that drugs that produce conditioned place preference will also induce conditioned taste aversion (e.g., Cunningham et aI., 1991;Reicher & Holman, 1977;Smith & Holman, 1987). Indeed, several studies from this laboratory have shown that the same dose ofethanol as that used here establishes a robust conditioned taste aversion in DBA/2 mice (Risinger & Cunningham, 1992b, 1995.…”

“…This apparent paradox has been interpreted in several different ways. One approach, derived from the principle of selective association, is to propose that the drug is simultaneously rewarding and aversive and that exteroceptive and gustatory cues are differentially associated with these opposite motivational effects (Reicher & Holman, 1977). A second approach argues that performance in both tasks actually reflects learning about the same underlying positive motivational effect (Hunt & Amit, 1987).…”

“…A Pavlovian analysis is also consistent with studies showing an influence ofthe temporal relationship between exposure to the environmental CS and drug US, The most commonly used temporal arrangement has involved "simultaneous" exposure to both events (i.e., the drug is injected immediately before placement of the subject in the CS environment). When exposure to the CS is delayed following drug administration (i.e., backward conditioning), conditioned place preference has sometimes been reported at intervals ofup to 2 h (but not 4 h) with an amphetamine US (Reicher & Holman, 1977;Sherman, Roberts, Roskam, & Holman, 1980; but see Wall, Hinson, Schmidt, Johnston, & Streather, 1990). With nicotine, however, backward intervals as short as 20 min have yielded no place conditioning (Fudala & Iwamoto, 1986).…”