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Is blockade of conditioned flavor aversions by chlorpheniramine the result of state dependency?

Conditioned flavor aversions induced by pairing flavored fluids with ionizing irradiation, lithium chloride, estrogen, or centrifugal rotation have been blocked by prior administration of chlorpheniramine. The blockade may be due to state dependency. This possibility was evaluated in the present experiment, which assigned female Long-Evans rats to a factorial combination of chlorpheniramine (20 mg/kg) vs saline during training, centrifugal rotation (150 rpm for 15 min) vs none as an UCS, and chlorpheniramine vs saline in testing. Rats conditioned with saline and rotation showed strong aversions when tested with either same or chlorpheniramine. Rats conditioned with chlorpheniramine and rotation showed no change during conditioning; when tested with saline they showed no aversion, and when tested with chlorpheniramine they showed no change from conditioning. Rats conditioned with either chlorpheniramine or saline and no rotation showed high fluid intake when tested with saline and reduced fluid intake when tested with chlorpheniramine. The results were interpreted as offering little support for state dependency.

Animals↗

Differential effects of subdiaphragmatic vagotomy on NaCl-induced aversion learning.

The vagus nerve has been proposed in numerous studies as one of the peripheral mechanisms involved in drug-induced taste aversion learning, although available data have been controversial. The differential results obtained in the present series of experiments with vagotomy and NaCl-induced short-term and long-term aversion learning suggest that the vagal system plays a decisive role in tasks requiring the rapid detection of an aversive substance in the gastrointestinal tract (short-term tasks). In contrast, this mechanism appears to be unnecessary in long-term tasks, where learning may be mediated by alternative slower-acting peripheral mechanisms such as the humoral system.

Animals↗

Reinstatement of latent inhibition following a reminder treatment in a conditioned taste aversion paradigm.

Reminder treatments have been shown to facilitate the retrieval of a variety of conditioned responses. Whether or not similar results would occur with an experimental paradigm which involves primarily memory for a stimulus, i.e., where no particular response is specified, is unclear. Accordingly, using Sprague-Dawley rats, we employed a latent inhibition paradigm with a long (10 days) retention interval between sucrose (CS) preexposure and sucrose-illness pairing (training). The results demonstrated a loss of latent inhibition following the 10-day retention interval suggesting "forgetting" of the CS preexposure. However, placing a single reminder exposure to the CS within the preexposure-to-training interval reinstated the preexposure effect. Controls indicated that in the absence of the initial preexposure the reminder per se did not produce latent inhibition. Thus, a reminder can reinstate a stimulus attribute (flavor representation) and explicit conditioned responses.

Animals↗

Enhancement of sensory preconditioning by a moderate dose of ethanol in infant and juvenile rats.

Little is known regarding the effects of acute ethanol on learning and memory among infant and juvenile rats. Two experiments were designed to evaluate the influence of various doses of ethanol administration on sensory preconditioning and primary conditioning in preweanling (16-day-old) and postweanling (28-day-old) rats. Moderate doses of ethanol facilitated conditioning at both ages. In the absence of ethanol, sensory preconditioning was not statistically significant among postweanlings in Experiment 1, although the phenomenon was clear and robust among preweanlings. Sensory preconditioning was facilitated by administration of doses of 0.8 and 1.2 g/kg ethanol in preweanlings and a dose of 1.6 g/kg ethanol in postweanlings, whereas sensory preconditioning was impaired in preweanlings by a high dose (2.4 g/kg) of ethanol. This reflected a shift to the right, between the preweaning and the postweaning periods, in the dose-response curve. It was determined in Experiment 2 that the effect of ethanol on sensory preconditioning could not be explained by stimulus generalization or an effect of ethanol on first-order conditioning, confirming the effect of ethanol on learning of the odor-odor association in the preexposure phase. The basis for a dose-dependent biphasic effect of ethanol on sensory preconditioning is discussed.

Animals↗

Attenuation of sensory preconditioning by noradrenaline depletion in the rat.

In order to investigate the effect of noradrenaline (NA) depletion upon an associative learning phenomenon, sensory preconditioning, rats were inflicted with either 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or with systemic injections of the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Using appropriate controls (the UP groups) sensory preconditioning was demonstrated clearly in the non-lesion conditions (Sham or saline), but was blocked or strongly attenuated in the DNAB and DSP4 conditions. LC lesions did not affect sensory preconditioning. These findings suggest that the loss of central NA may cause some disruption of some aspects of complex associative learning. The role of NA in sensory preconditioning may be relevant to current notions of NA function.

Animals↗

Attenuation of neophobia and conditioned taste aversion in the rabbit.

The phenomenon of taste neophobia to apple juice does exist in the rabbit. It was found that malic acid was the main stimulus source. Attenuation of taste neophobia was due to neuronal processes which took place between rather than during drinking sessions. Conditioned taste aversion learning took place if apomorphine was injected after apple juice intake.

Animals↗

Electrical intracerebral stimulation of the area postrema on taste aversion learning.

The structural characteristics of the area postrema, its anatomical connections, participation in the detection of emesis-provoking substances and the effects of area postrema lesions on taste aversion learning acquisition, are all factors which speak in favor of a role as a chemoreceptor zone involved in the detection of aversive agents which act as effective inducers of taste aversion learning. The feasibility of substituting electrical intracerebral stimulation of the area postrema for the aversive stimulus was investigated in a taste aversion learning paradigm. In Expt. 1, 0.1-ms rectangular pulses of 50 Hz, delivered intermittently or continuously for 4 h after a 15-min delay following ingestion of the gustatory stimulus, produced reliable learning. Expt. 2 showed the learning thus induced to reflect all the characteristics features attributed to taste aversion learning: one-trial learning, long interstimulus delay and cue-consequence specificity. These results suggest that the area postrema could participate in the detection of the aversive consequences of particular taste aversion learning-inducing agents.

Animals↗

Universality of parabrachial mediation of conditioned taste aversion.

Disruption of conditioned taste aversion (CTA) by tetrodotoxin (TTX) blockade of parabrachial nuclei elicited after ingestion of the gustatory CS and before administration of the visceral US is revealed by unchanged CS preference in retrieval test performed two days after acquisition. The universality of the above amnesia was examined in rats. In Experiment 1, parabrachial TTX disrupted CTAs when sodium saccharin (0.1%), quinine hydrochloride (0.0072%), sodium chloride (0.9%) or a garlic extract were used as the CS and i.p. LiCl (0.15 M, 2% body weight) as the US. In Experiment 2, parabrachial TTX disrupted CTAs when 0.9% NaCl was used as the CS and i.p. injection of LiCl (0.15 M, 2% body weight), D-amphetamine (3 mg/kg) or carbachol (0.15 mg/kg) served as the US. Experiment 3 showed that post-drinking parabrachial TTX blocked also CTA induced by LiCl drinking, i.e. under conditions of CS-US identity. Experiments 4 and 5 demonstrated that the amnesia is not confounded by TTX-induced reduction of fluid intake because the CTA disruption was well expressed even when tested after recovery of normal fluid intake 3 days after TTX injection and in animals receiving 12 days of preacquisition adaptation to limited fluid access. It is concluded that parabrachial nuclei represent an important point of convergence for various classes of CTA eliciting stimuli.

Afferent Pathways↗

Prefrontal cortex and the relative associability of taste and place cues in rats.

The effects of cutting the corticocortical connections between medial and sulcal prefrontal areas on the conditioning of taste and place cues were examined. In Experiment 1, rats were simultaneously exposed to taste and place cues before injection of 0.15 M LiCl. In controls, a significant conditioned taste aversion (CTA) but no conditioned place aversion (CPA) was observed. In contrast, rats with bilateral knife cuts showed a significant CPA but a weaker CTA. To test whether these results could have been due to the effects of simultaneously exposing the rats to taste and place cues during conditioning, rats were trained independently in either CTA or CPA paradigms in Experiment 2. In the CTA test, rats both in operated and control groups showed a CTA when first tested. Rats with bilateral knife cuts, however, showed a weaker CTA than those in the control group. In the CPA test, rats in the control group did not exhibit a CPA, whereas the knife cut group did. Rats with sham lesions tested in Experiment 2 did not differ from control subjects on either the CPA or the CTA test. Thus, bilateral cuts increased the CPA and decreased the CTA even when tested independently. These results indicate that the relative ease of association of place and taste stimuli may be accounted for in part by the organization of the intrinsic connections of the prefrontal cortex in the rat.

Animals↗

Nucleus basalis magnocellularis lesions impair mossy fiber system in rat hippocampus: a quantitative histochemical and ultrastructural study.

Lesions of the nucleus basalis magnocellularis (NBM) cause depletion of choline acetyltransferase (ChAT) in the cerebral cortex and behavioral changes consisting of impaired ability to learn avoidance tasks. Since hippocampal mossy fibers (MF) are involved in the elaboration of passive avoidance responses, we analyzed MF by means of Timm's histochemical technique and electron microscopy, to find out whether monolateral lesions of NBM had any effect on MF system. NBM-lesioned rats, 3 weeks after lesioning, showed a significant and progressive decrease in the density of Timm staining as well as significant changes of the morphology of synapic boutons of the MF. These results suggest that, although NBM does not send direct projections to the hippocampus, lesions of this nucleus may have a neurodegenerative effect on the intrahippocampal pathway involved in avoidance responses.

Journal Article↗

Exercise quotas, anticipatory concern and self-efficacy expectancies in chronic pain: a preliminary report.

Reduced activity levels are a frequently encountered problem among chronic pain patients which has been shown to be responsive to exercise quota systems. This study extends the knowledge of exercise quota systems by examining their effects on beliefs relevant to exercise avoidance. Results indicate that exercise quota systems produce systematic increases in both exercise levels and expectancies of capability while reducing worry and concern about exercising. These data highlight the importance of avoidance learning in chronic pain and suggest that the effectiveness of exercise quota systems is related to a deconditioning process based on exposure rather than the process of applying reinforcement to quota achievement.

Adult↗

Differential involvement of hippocampal G-protein subtypes in the memory process of rats.

Inactivation of Gi and G(o) proteins in the dentate gyrus of the hippocampus by pertussis toxin did not affect memory retention of a one-way passive avoidance learning task in rats. Interference of normal Gs activity in the dentate gyrus by cholera toxin impaired retention performance dose-dependently. Cholera toxin also antagonized the memory-enhancing effect of corticotropin-releasing factor in the hippocampus. However, although Gi and G(o) proteins are probably not involved in the memory consolidation process per se, in animals showing a full retention score there was a significant and long-lasting increase of G(o) concentration in the dentate gyrus. Results of ADP-ribosylation experiments have shown that there was a dose-dependent decrease of ADP-ribosylation in vitro as the concentration of in vivo pertussis toxin and cholera toxin increased. These results together suggest that Gs protein is probably involved in the initiation of the memory consolidation process, while enhanced G(o) expression is the ultimate result upon memory formation. These results provide the first in vivo evidence relating the functions of hippocampal G proteins to the memory process of mammals.

Animals↗

Posterior hypothalamic deafferentation abolishes the amnestic effect of electroconvulsive shock in rats.

The amnestic effect of immediate post-training transcorneal electroconvulsive shock ECS (15.0 mA, 60 Hz, 2 sec) on step-down inhibitory avoidance learning (0.5 mA, 60 Hz training footshock) was studied in intact rats and in rats submitted to bilateral surgical transection of the dorsal fornix, to anterior or posterior hypothalamic deafferentation, and in sham-operated animals. Animals were tested for retention 24 hr after training. The amnestic effect of ECS was observed in all groups except in the one with the posterior hypothalamic lesion. Fornix-lesioned animals showed a moderate retention deficit which was considerably worsened by the ECS treatment. The results indicate that the amnestic effect of ECS requires integrity of posterior hypothalamic pathways. One possibility is that the amnestic effect of ECS may be mediated by posterior afferent fibers to the hypothalamus acting on hypothalamic opioid systems such as have been previously proposed to play a role in ECS-induced amnesia.

Afferent Pathways↗

Alcohol and taste-mediated learning.

Taste-mediated learning is relevant to the alcohol consumption patterns of animals. This review concludes that taste aversion learning has thus far prevented development of an animal model of alcoholism. The presence of a taste cue, lack of control over alcohol administration, and high alcohol concentrations or dosages all facilitate the development of alcohol aversions. There is little evidence that taste preference learning is involved in the development of alcohol dependence. Data from taste-mediated learning research with animals are consistent with drinking patterns of human alcoholics.

Alcohol Drinking↗

Diphenylhydantoin facilitation of labile, protein-independent memory.

Diphenylhydantoin (DPH 10(-4)M) administered subcutaneously to chicks 5 min after a one-trial passive avoidance learning task successfully counteracted amnesia induced by pretreatment 5 min before learning with ouabain or cycloheximide (CXM). Biochemical assays confirmed that in chick forebrain homogenate DPH at concentrations of 1 and 5 X 10(-4)M enhanced Na+/K+ ATP'ase activity. Since both DPH and ouabain inhibit post-tetanic potentiation, the results support the hypothesis of an initial labile phase of memory based on sodium pump (Na+/K+ ATP'ase) activity. DPH was less effective in counteracting ouabain-induced amnesia if administered later than 10 min after learning and CXM-induced amnesia if administered later than 30 min after learning. This suggests that the effect of DPH on CXM-induced amnesia is through enhancement of Na+/K+ ATP'ase activity. It was suggested that the possible hyperpolarization of membrane potential associated with sodium pump activity may serve to mark the labile memory trace, enabling formation of a more permanent trace through protein synthesis.

Adenosine Triphosphatases↗

Behavioral effects of lesions of precommissural and postcommissural fornix.

Lesions which sever different parts of precommissural or postcommissural fornix were compared to the effects of control lesions in several behavioral tasks. Spatial learning and avoidance was impaired by lesions of the descending columns, or by lesions which sever the precommissural communications passing to and from medial septum. Damage to precommissural fibers through lateral septum produced a measurable change only on the avoidance task. This pattern of deficits, considered together with the anatomical relationship of the system, suggests a model in which the medial septum relays kinesthetic information to dorsal hippocampus, which in turn serves as a memory system in the performance of spatial habits. It is less clear what kind of information is relayed by lateral septum, but it may communicate with ventral hippocampus regarding the consequences of punishment, and thus serve as part of a system for defensive suppression of behavior.

Animals↗

Neocortical involvement in the acquisition and retention of learned alcohol aversions in rats.

In one experiment, rats lacking gustatory neocortex (GN) were compared with control (both normal and control lesion) rats in the acquisition of a learned alcohol aversion. In a second experiment, the effect of GN ablations on preoperatively learned alcohol aversions was examined. Results showed that rats lacking GN both learned and retained alcohol aversions in a normal manner. These same GN rats, however, extinguished the alcohol aversions significantly faster than controls. These results are in contrast to previous data which indicated that the integrity of the GN was necessary for normal acquisition and retention of learned taste aversions. It is suggested that the odor qualities present in the alcohol stimulus account for the relatively normal performance of GN rats.

Alcohol Drinking↗

Alcohol and the brain: setting the benefit/risk balance.

This article reviews the literature and presents some unpublished data on the CNS effects of alcohol at doses not producing tolerance and dependence. The available evidence indicates that the effect of low doses of ethanol may qualitatively differ from those produced in animal models mimicking alcoholism. For example, rats exposed for two months to alcohol in drinking water at a concentration (3%) not inducing tolerance or dependence, as assessed by lack of withdrawal signs upon treatment suspension, appear to be less stressed in the two-way avoidance-learning tests. Accordingly, the treated rats perform better and learn faster than sucrose-fed controls, while this behavior is disrupted by high levels of ethanol intake. These initial observations suggest that discontinuity may exist between the effects of low and high doses of this substance and underscore the need to expand research on the effects of alcohol on the CNS to include the bottom end of the dose-response curve.

Alcoholism↗