Milagros Gallo

Differential involvement of gustatory insular cortex and amygdala in the acquisition and retrieval of conditioned taste aversion in rats

Lesion studies of the role of the gustatory insular cortex (GC) and amygdala (Am) in conditioned taste aversion (CTA) are confounded by the irreversibility of the intervention. Functional ablation methods allow more specific influencing of different phases of CTA acquisition and retrieval. Bilateral tetrodotoxin (TTX) blockade of GC (10 ng) or Am (3 ng) before or after saccharin drinking in rats with chronically implanted intracerebral cannulae showed that GC is indispensable for the initial processing of the taste stimulus but not for the association of the gustatory trace with the symptoms of LiCl poisoning. Gustatory signals can by-pass the blocked Am, the inactivation of which, however, impairs the gustatory trace-poisoning association. TTX injection into both GC and Am impairs CTA retrieval more than isolated blockade of either of these structures. It is argued that GC and Am implement processing of gustatory and visceral signals, respectively, but that formation and consolidation of the CTA engram proceeds outside forebrain, probably at the level of the brainstem.

The functional relevance of the lateral parabrachial nucleus in lithium chloride-induced aversion learning

Lesions to the lateral parabrachial nucleus (PBN), one of the subnuclei that make up the pontine parabrachial complex, impairs the acquisition of taste aversion learning (TAL) with LiCl as the toxic stimulus. In this experiment, PBNl-lesioned and control rats were trained to learn a delayed task with a 15-min interval between presentation of the gustatory and the aversive stimulus. The impairment in learning observed after lesions of the PBNl is discussed in terms of disruption of the transmission of toxic stimuli (LiCl) processed by the humoral pathway and the area postrema (AP).

Lesions of the lateral parabrachial nuclei disrupt aversion learning induced by electrical stimulation of the area postrema

The research about the neural basis of taste aversion learning (TAL) has pointed out the area postrema (AP) as a fundamental structure implied in the processing of certain toxic stimuli. Likewise, recent studies demonstrated that electric stimulation of the AP is an efficient substitute of the aversive stimulus. The lateral parabrachial nucleus (PBN1), one of the subnuclei of the parabrachial complex, is the main anatomic rostral connection of the AP. In the experiment presented here, we demonstrate that TAL induced by electric stimulation of the AP is interrupted when the PBN1 is lesioned, thus giving support to the functional role of this anatomic system (AP-PBN1) in the codification of aversive stimuli processed by the AP.

Patterns of Ethanol Intake in Preadolescent, Adolescent, and Adult Wistar Rats Under Acquisition, Maintenance, and Relapse‐Like Conditions

BACKGROUND Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption/preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective. METHODS Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured. RESULTS During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g/kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged. CONCLUSIONS In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment.

Reversible inactivation of dorsal hippocampus by tetrodotoxin impairs blocking of taste aversion selectively during the acquisition but not the retrieval in rats.

The role of the dorsal hippocampus in the different stages of blocking was examined in a taste aversion learning task. Blocking is a learning effect in which one previously conditioned element of a compound makes the conditioning of the added element difficult. An effective blocking procedure with one trial in each stage was tested in unoperated rats. In the first stage, rats drank saccharin and later received lithium chloride by i.p. injection. In the second stage, they were presented with a serial compound saccharin-cider vinegar before lithium injection. In a one-bottle, test a reduced aversion to cider vinegar was observed in this group compared to control groups with no previous saccharin aversion. Bilateral tetrodotoxin (TTX) injection (10 ng/microliters) in the dorsal hippocampus attenuated blocking if this was applied before drinking the compound stimulus during the second stage, but it produced no effect applied either before drinking saccharin in the first stage or before testing. Non-specific retrieval deficit produced by TTX injection applied before testing was ruled out in a control group subjected to a conventional cider vinegar aversion learning which showed complete retrieval of the aversion under TTX. It is concluded that the hippocampal function relevant for blocking takes place during the compound phase.

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.

Effects of medullary afferent vagal axotomy and area postrema lesions on short-term and long-term NaCl-induced taste aversion learning

This series of experiments demonstrates a functional dissociation between the area postrema (AP) and the vagus nerve in short-term taste aversion learning (TAL). Although medullary axotomy of the afferent component of the vagus disrupted the learning observed with NaCl-induced short-term (nondelayed) TAL, lesioning the AP failed to interfere with the discriminative process employed by the animals under the same conditions. However, involvement of neither the vagus nerve nor the AP seemed to be indispensable for learning in NaCl-induced long-term (delayed) TAL. The possibility that the vagus nerve and the AP are involved in temporally distinct visceral processing is discussed.

The functional relevance of the area postrema in drug-induced aversion learning

Research into the neural mechanisms involved in the acquisition of learned aversions induced by drug points toward the area postrema (AP) as one of the structures implicated in the detection of drug aversive consequences. The evidence suggest that although the AP is indeed involved in drug-induced learned aversions, its functional integrity is not always a necessary requisite for learning to take place. The aim in this study was to determine whether the AP is essentially or selectively involved in all learned aversions induced by scopolamine methyl nitrate (SMN) using different number of trials with the aversive stimulus. In Experiment 1, AP-lesioned rats were injected with SMN fifteen minutes after consuming a flavoured solution during three consecutive trials. A single-stimulus test failed to detect learned aversions, which were, however, evident in two subsequent choice-tests. In one-trial paradigms, however, choice-tests as well as single-stimulus tests failed to detect learned aversions in AP-lesioned rats, both when SMN was injected immediately after stimulus intake (Experiment 2) and when a fifteen-minute delay was introduced (Experiment 3). The results suggested that the AP is not essential for the acquisition of SMN-induced aversion learning with three consecutive trials if learning is detected with a choice-test, although effective single-trial learning does apparently require a functional AP.

Tetrodotoxin inactivation of the gustatory cortex disrupts the effect of the N-methyl-d-aspartate antagonist ketamine on latent inhibition of conditioned taste aversion in rats

The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine on latent inhibition of taste aversion learning was studied in rats. Systemic injections of ketamine (50 mg/kg) applied after each of three preexposures to sodium saccharin (0.1%) disrupted the latent inhibition effect. The blockade was not due to aversive properties of ketamine, because three saccharin-ketamine pairings did not produce saccharin aversion. Moreover, the ketamine-induced blockade of latent inhibition was disrupted by tetrodotoxin injections (10 ng/microl)-induced reversible inactivation of gustatory cortex, applied after each preexposure. A specific gustatory cortex mediation of the ketamine effect is discussed.

Acquisition of conditioned taste aversion in rats is mediated by ipsilateral interaction of cortical and mesencephalic mechanisms

The possibility to lateralize the neural circuits mediating conditioned taste aversion (CTA) has been examined by combination of functional hemidecortication and unilateral tetrodotoxin (TTX) injection into the parabrachial nucleus (PBN). Rats drinking saccharin (CS) during cortical spreading depression (CSD) in the right hemisphere and receiving unilateral PBN injection of TTX (3 ng) shortly before i.p. injection of lithium chloride (LiCl) (US) formed CTA when CSD and TTX were applied to the same hemisphere but not when applied to different hemispheres. Rats drinking saccharin with intact brain and receiving unilateral TTX overlapping with LiCl administration learned a weak CTA, the retrieval of which was disrupted by either ipsilateral or contralateral CSD during retention testing. It is concluded that CTA acquisition requires cooperation of ipsilateral cortical and subcortical centers but that formation of unilateral subcortical CTA engram does not warrant lateralization of the retrieval process.