Discriminated Taste Aversion Research Articles

Discriminative stimulus effects of the cannabinoid CB1 receptor antagonist rimonabant in rats

To examine the discriminative stimulus effects of the cannabinoid CB(1) receptor (CB(1)R) antagonist/inverse agonist rimonabant (SR141716A) using a discriminated taste aversion (DTA) procedure. Groups of rats were trained to discriminate between drug (5.6 or 3 mg/kg) and vehicle in DTA (t' = 20 min). The 30-min drinking opportunity after rimonabant pretreatment was followed by injection of lithium chloride (120 mg/kg) in the experimental (EXP) animals. When offered fluid after vehicle pretreatment, EXP animals subsequently were given intraperitoneal saline (NaCl, 10 ml/kg). Post-drinking treatment for controls (CONT) was NaCl irrespective of the pretreatment condition (rimonabant or vehicle). Tests examined other doses and drugs (t' = 20 min). The rimonabant analog AM251 (1 to 5.6 mg/kg) substituted for rimonabant. AM281 also appeared to substitute, but interpretation is complicated by unconditioned effects (drinking suppressed also in the CONT group). The CB(2)R antagonists SR144528 (18 and 30 mg/kg), AM630 (1 to 10 mg/kg), and the CB(1)R agonist methanandamide (mAEA, 3 and 10 mg/kg) did not substitute. There was a dose-related attenuation of the rimonabant-induced suppression of saccharin drinking when Delta9-tetrahydrocannabinol (Delta9-THC; 0.3 to 5.6 mg/kg), but not mAEA (1 to 10 mg/kg), was given together with rimonabant (3 mg/kg). Unconditioned effects occurred with the mAEA-rimonabant combination, not evident for combinations of rimonabant and Delta9-THC. mAEA (10 mg/kg) plus AM251 (5.6 mg/kg) resulted in strong unconditioned effects. Rimonabant induces a discriminative stimulus in DTA that continues to show potential for further examination of cannabinoid receptor antagonism.

Discriminative taste aversion learning: A learning task for older chickens

The study of learning and memory using the chicken model has relied on three learning paradigms, passive avoidance learning, imprinting and the pebble floor task. Passive avoidance learning and imprinting have been used predominantly in very young chickens and cannot be used to access learning and memory in older chickens. We have established a new behavioural learning paradigm, Discriminative Taste Aversion Learning (DTAL), that can be used with both young and older animals. The task requires chickens to discriminate between food crumbs dyed either red or yellow with one colour being associated with the aversive tasting substance, methylanthranilate. Learning can be tested at various times after the training session by presenting chickens with the coloured food crumbs without an aversive taste. Both chickens tested at 5 and 15 days post-hatch learned to avoid the aversive crumbs. Furthermore, the protein synthesis inhibitor anisomycin (30 mM; 10 μl per hemisphere) injected into the intermediate medial hyperstriatum ventrale 15 min pre-training or 45 min post-training blocked long-term memory for the DTAL task when tested 24 h later. Memory for the task was unaffected by anisomycin injection 120 min post-training or in control animals injected with saline at similar times. The timing of the cellular processes of protein synthesis needed for consolidation of the DTAL appears to be similar to those described for the other behavioural paradigms in young chickens.

Effects of ethanol on an acetaldehyde drug discrimination with a conditioned taste aversion procedure

The current study was designed to investigate whether ethanol shares stimulus properties with acetaldehyde with the use of a discriminative taste aversion procedure. Animals were trained to discriminate a dose of acetaldehyde (0.2 or 0.3 g/kg, i.p.) from saline in eight consecutive cycles consisting of a pairing day (PD) and three nonpairing days (NPDs). On PDs, all animals were injected with a particular dose of acetaldehyde 30 min before a 20-min limited access to a saccharin solution [0.1% (wt./vol.)] and then injected immediately with either LiCl (0.15 M, 1.8 mEq) or saline. On the three following NPDs, animals were injected with saline and 30 min later were presented with the same saccharin solution for 20 min. All animals in each acetaldehyde training dose group acquired discriminative stimulus control before generalization tests were conducted. Results of generalization tests (ethanol doses of 0.8, 1.2, 1.6, and 2.0 g/kg) revealed that ethanol substituted for acetaldehyde at doses of 1.2 and 1.6 g/kg for both training doses of acetaldehyde. The findings for this study indicate that acetaldehyde and ethanol may share some stimulus properties.

Discriminated Taste Aversion and Context: A Progress Report

JÄRBE, T. U. C. AND R. J. LAMB. Discriminated taste aversion and context: A progress report. PHARMACOL BIOCHEM BEHAV 64(2) 403–407, 1999.—The research described here concerns the interaction between the environment (context), the organism, and the effects of opiates, focusing on how conditioning and contextual cues affect drug controlled behaviors. This analysis applies the powerful tool of drug discrimination to a respondent conditioning procedure (discriminated taste aversion, DTA). Data show that the use of DTA is feasible in that it is sensitive to morphine dose and saccharin concentration. Swifter control over DTA was achieved by increasing the LiCl dose (UCS magnitude). It is also clear that morphine alone can serve as a discriminative stimulus not requiring saccharin as a contextual element (which has been the case for most DTA studies to date), or saccharin being part of a compounded stimulus. Pharmacological specificity was demonstrated in substitution tests with delta-9-tetrahydrocannabinol. This research continues a systematic experimental analysis of the interaction between drug-controlled behavior and context.

Effects of lithium dose (UCS) on the acquisition and extinction of a discriminated morphine aversion

The effects of varying the lithium dose (unconditioned stimulus [UCS]; LiCl range 30-180 mg/kg) on the acquisition and extinction of stimulus control by 5.6 mg/kg of morphine in a discriminated taste aversion (DTA) procedure were examined in rats. In addition, pharmacological specificity was examined by substituting (-)-delta-9-tetrahydrocannabinol (delta9-THC) for morphine during a test phase intervening between acquisition and extinction. DTA acquisition was more rapid at higher LiCl doses. The lowest dose of LiCl, 30 mg/kg, did not robustly maintain a DTA. Two groups treated with 60 mg/kg LiCl, differing only in the type of drinking nozzle used (ball-bearing vs standard non-ball-bearing), behaved similarly. Suppression of drinking was related to the morphine dose, in an orderly manner (dose range 0.3-10 mg/kg), in rats for which morphine was followed by LiCl. No significant decline in drinking occurred for rats for which morphine was followed by saline, except perhaps at the 10 mg/kg test dose of morphine. The control of drinking was pharmacologically specific; both experimental and control animals were equally affected in tests with delta9-THC (0.3-10 mg/kg). Low doses of delta9-THC increased water consumption; this did not occur with morphine. During extinction the reinstitution of drinking was similar across groups that had been effectively conditioned, i.e. there was no apparent effect of lithium dose on extinction. After extinction, a much attenuated reaction occurred to morphine in tests with 3 and 10 mg/kg. These doses of morphine had significantly suppressed drinking before the extinction phase. Collectively, these data add to the formal similarities between sensory and drug discriminative stimuli.

Multielemental stimulus control: effects of saccharin concentration on a discriminated morphine-saccharin taste aversion.

The effects of saccharin concentration on the stimulus control by a compound stimulus consisting of morphine, saccharin (0.01, 0.03, or 0.10%, wt/vol), and a ball bearing drinking nozzle in a discriminated taste aversion (DTA) procedure were examined in rats (Rattus norvegicus). In paired rats injections of lithium followed presentation of this compound stimulus, whereas in unpaired rats saline injections followed this stimulus. DTA acquisition was more rapid at higher saccharin concentrations. In testing with each individual stimulus element, stimulus control was clearly exerted by all 3 stimulus elements. When another stimulus element was presented jointly with saccharin, behavioral control was similar to that of saccharin alone. Behavioral control by saccharin increased with saccharin concentration. However, behavioral control by the 2 other stimulus elements was relatively unaffected when the saliency of the saccharin element was increased.

Discriminated conditioned taste aversion for studying multi-element stimulus control

The effects of morphine pre-treatment interval on the stimulus control exerted by a multi-element stimulus consisting of morphine (5.6mg/kg), saccharin (0.2%, w/v), and a ball-bearing drinking nozzle in a discriminated taste aversion procedure were examined. In this discriminated aversion procedure, rats received injections of LiCI following presentation of this multielement stimulus, and injections of saline following the saline, water, and non-ball-bearing nozzle composite stimulus. These paired rats were compared to unpaired rats that received saline injections rather than LiCI injections following presentation of the multi-element stimulus. Morphine pre-treatment times of 5, 10, and 20min were examined in groups of 12 paired and 6 unpaired rats. The discrimination was rapidly learned under all three pre-treatment intervals. In subsequent testing with each individual stimulus element and combinations of two stimulus elements, stimulus control was clearly exerted by both morphine and saccharin. Paired rats drank less saccharin than unpaired rats, and less saccharin than water. Similarly, paired rats drank less fluid following morphine administration than following saline administration, and less fluid than unpaired rats following morphine administration. Control by the nozzle type was also apparent in significant interactions between the nozzle and morphine or saccharin and pairing with LiCI. In general, pre-treatment time did not influence the stimulus control that developed. However, at the two shorter pre-treatment times there was some indication that a conditioned taste aversion to morphine was developing in the unpaired rats. These experiments indicate that such discriminated taste aversion procedures may be viable methods for studying the contextual control of how drugs function as discriminative stimuli, and that longer drug pre-treatment times may be desirable in such procedures.

Antidepressant-like behavioral effects of serotonin receptor agonists

The clinical discoveries that drugs that stimulate 5-HT neurotransmission, either by inhibiting 5-HT uptake or by stimulating postsynaptic receptors directly, have antidepressant properties has stimulated interest in defining the role of the 5-HT receptor system in the clinical effects of antidepressant drugs. Two approaches are reviewed in this paper that address the neurochemical mediation of the therapeutic effects of antidepressant drugs from the standpoint of animal behavior. The first approach utilizes a behavioral response in rats, the forced swimming test, that correlates well with predicting antidepressant drugs in humans. Studies are reviewed that examined serotonergic compounds in the forced swimming test, from the standpoint of identifying better serotonergic mechanisms involved in the antidepressant response. Both 5-HT uptake inhibitors and 5-HT 1A receptor agonists produce effects in the forced swimming test that are similar to those of other classes of antidepressant drugs. In contrast, agonists at other 5-HT receptors or 5-HT receptor antagonists do not produce antidepressant-like behavioral effects. Evidence for an important role of 5-HT 1A receptors in the antidepressant response is supported by findings that antagonists of 5-HT 1A receptors prevent the ability of 5-HT 1A receptor agonists to reduce immobility in the forced swimming test. The results of studies interfering with 5-HT neurotransmission, either by inhibition of 5-HT synthesis or by the destruction of 5-HT neurons, favor the idea that the effects of 5-HT 1A receptor agonists are produced by the stimulation of postsynaptic 5-HT 1A receptors. The second approach for studying the behavioral effects of antidepressant drugs employs drug discrimination studies, conducted using a discriminated taste aversion procedure, to provide a method for studying the discriminative stimulus effects of the antidepressant 5-HT uptake inhibitor sertraline. Rats were trained to discriminate the effects of sertraline (10 mg/kg) from saline. Other 5-HT uptake inhibitors, such as fluoxetine, fluvoxamine and paroxetine, substituted for the sertraline stimulus. High doses of norepinephrine uptake inhibitors, such as desipramine or maprotiline, were required to produce similar effects. These two behavioral approaches promise to be useful for defining the important pharmacological effects associated with the behavioral effects of antidepressant drugs.

Discriminative stimulus properties of the benzodiazepine receptor antagonist flumazenil.

Rats were trained to discriminate the stimulus properties of the benzodiazepine (BZ) receptor antagonist flumazenil using a conditioned taste aversion procedure. On drug trials, fluid-restricted rats were injected with flumazenil (32 mg/kg), given access to a 0.25% saccharin solution for 30 min, and injected with LiCl (1.8 mEq/kg IP). On saline trials, injections of saline bracketed the period of saccharin consumption. Acquisition of the discriminated taste aversion, as measured by differential effects on drinking between saline and drug trials, developed after only five pairings of flumazenil with the LiCl injections. Flumazenil did not alter saccharin consumption in unconditioned controls (N = 9) that never received LiCl. The discrimination was also measured by flumazenil's ability to reduce the preference for saccharin over tap water using two-bottle choice tests. Flumazenil demonstrated dose-dependent generalization upon decreasing the training dose as low as 1 mg/kg. Two other BZ receptor antagonists of different chemical structure, CGS 8216 and ZK 93426, substituted completely for the flumazenil stimulus. Partial generalization was exhibited to the partial inverse agonists FG 7142 and beta-CCE, while the full inverse agonists DMCM and PTZ failed to substitute for the flumazenil stimulus. The BZ receptor agonists diazepam and alprazolam failed to substitute for the flumazenil stimulus, although partial generalization was shown with CDP. The results suggest that the BZ receptor antagonist flumazenil may produce intrinsic discriminative stimulus effects that are independent from those of BZ receptor agonists or inverse agonists.

Discriminated taste aversion with a 5-HT agonist measured using saccharin preference

Rats were trained to discriminate the stimulus properties of the selective 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.4mg/kg i.p.) versus saline, using a discriminated taste aversion procedure. Tests of stimulus generalization and drug substitution were conducted using two-bottle choice tests between saccharin and water. Rats that received pairings of 8-OH-DPAT with LiCl demonstrated significant reductions of saccharin preference when administered 8-OH-DPAT at doses of 0.1mg/kg or higher. 8-OH-DPAT did not alter saccharin preference significantly in controls that did not receive LiCl injections. Other drugs with high affinity for 5-HT(1A) receptors, such as the azapirones gepirone, ipsapirone and buspirone, produced selective reductions of saccharin preference in rats trained to discriminate 8-OH-DPAT from saline but not in controls. Three drugs with low affinity for 5-HT(1A) receptors, the benzodiazepine anxiolytic diazepam, d-amphetamine, and a common metabolite of the azapirones 1-(2-pyrimidinyl) piperazine (1-PP) altered fluid intake significantly but failed to produce significant changes in saccharin preference in either the discrimination or control groups. This study indicates that two-bottle preference tests can be used to measure the stimulus properties of 8-OH-DPAT trained using a discriminated taste aversion procedure, because the stimulus effects of drugs, measured using saccharin preference, can be separated from the nonspecific effects of drugs on fluid consumption.

Discriminated taste aversion with chlordiazepoxide

Discriminative stimulus effects have been studied extensively with the two-response, food-reinforced operant procedure and more recently also with discriminated taste aversion (DTA) procedures. DTA procedures have the advantage of a more rapid discrimination training. However, the test phase, i.e., drug substitution, of the DTA procedure is more time consuming (1 test per 4 days) than the test phase of the two-response procedure (2 tests per 5 days). The present study investigated whether a DTA procedure with 2 tests per 5 days could be implemented. In addition, the specificity of the DTA procedure was investigated. Rats were trained to discriminate chlordiazepoxide (CDP, 20 mg/kg, IP) from vehicle using a discriminated taste aversion procedure. Selective suppression of saccharin consumption after CDP injections was maximal after seven CDP-LiCl pairings. In subsequent substitution tests, with 2 tests per 5 days, CDP-mimicking effects were found only for another benzodiazepine, diazepam, and for a barbiturate, pentobarbital. The results indicate that rats can be rapidly trained to discriminate CDP from vehicle in the discriminated taste aversion procedure and that the CDP-cue so produced has the same specificity as in a two-response, food-reinforced operant procedure. However, the DTA procedure has a number of drawbacks that make its advantage over the two-response procedure questionable.

Taste discrimination learning in preweanling rats

Seventeen-day-old rat pups received intraoral infusions of two novel flavors, coffee (0.625% w/v Sanka, decaffeinated) and saccharin (0.5% w/v), of which one (CS+) was paired with a 0.75% body weight, Lp. iiYection of 0.4 M LiCI, and the other (CS-) was presented alone. On the following day, two more infusion tests were conducted to determine intake of each flavor. Intake of the CS+ flavor was markedly suppressed, relative to that of the CS- flavor, although the magni­ tude ofthis effect depended on which flavor was designated CS+ and on the order in which CS+ and CS- were presented on the test day. These results indicate that preweanling rats are capa­ ble of discriminative taste aversion learning. This simple conditioning procedure should provide a useful method for studying the sensory development of the gustatory system and/or the de­ velopmental psychobiology of learning and memory.

Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats

Some recent studies on the discriminative stimulus (cue) and conditioned taste aversion (CTA) effects of nicotine are reviewed. The characteristics of the nicotine cue correlate well with those of high affinity nicotine binding in studies comparing different nicotinic agonists. The dose of nicotine used for training a discrimination is an important variable determining patterns of generalization. The effects of antagonists on the nicotine cue are also compatible with ligand-binding studies although the lack of competitive antagonists generates unsolved problems for investigators. The CTA produced by nicotine has pharmacological characteristics like the nicotine cue. Both effects are produced at CNS sites that resemble to a certain extent the cholinoceptive sites in autonomic ganglia. The small differences in the degree of stereoselectivity of the two effects or in their sensitivity to antagonists do not constitute substantive evidence for mediation by different receptors. The major differences between the procedures lies in their general psychopharmacological characteristics rather than in any special qualities of the response to nicotine. For example, the nicotine cue is not produced by agents from other pharmacological classes whereas a wide range of different drugs can produce CTA. The concept of multiple types of CNS nicotinic receptors, as supported by certain biochemical studies, requires further evaluation in behavioural systems.

Transfer of discriminated taste aversion to a leverpressing task

Rats were trained to avoid consuming saccharin (but not anise) by following saccharin consumption with apomorphine injections. The Ss later showed lower rates of leverpressing for saccharin than for anise or water. The results indicate that the saccharin taste had acquired generalized motivational properties.

Novelty vs temporal contiguity in learned taste aversions

Rats were administered apomorphine intraperitoneally following serial ingestion of saccharin and anise solutions. The animals had been previously familiarized with one of the solutions. An aversion to the novel stimuli developed independently of the flavor of the novel solution or of the order of presentation prior to apomorphine injection. Novelty was shown to be a more potent cue than was temporal contiguity in this particular conditioning of discriminated taste aversion. It was concluded that the long delays between CS and UCS presentation that have been found possible in the conditioned taste-aversion paradigm must be due to central processes and not to lingering aftertaste. Also, previously reported salience of certain tastes may be in part due to their novelty.