Conditioned Enhancement of Antibody Production Is Disrupted by Insular Cortex and Amygdala but Not Hippocampal Lesions

  title={Conditioned Enhancement of Antibody Production Is Disrupted by Insular Cortex and Amygdala but Not Hippocampal Lesions},
  author={Victor Ramirez-Amaya and Federico Berm{\'u}dez-Rattoni},
  journal={Brain, Behavior, and Immunity},
Pavlovian conditioning procedures can be used to activate the immune system. A reliable conditioned increase of antibody production can be obtained in rats that have previously received a gustative or odor stimulus as the conditioned stimulus paired with an antigen, by exposing the animals to the conditioned stimulus alone. We showed evidence that an excitotoxic lesion bilaterally applied into the insular cortex or the amygdala, but not into the dorsal hippocampus, impaired the acquisition of… 

Neural Substrates for Behaviorally Conditioned Immunosuppression in the Rat

The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.

Behavioral conditioning of the immune system.

Remembering immunity: Neuronal ensembles in the insular cortex encode and retrieve specific immune responses

It is shown that immune-related information is stored in the brain’s insular cortex (InsCtx) and that the brain can encode and initiate specific immune responses, extending the classical concept of immunological memory to neuronal representations of immunity.


Increased knowledge about the neuropsychological machinery steering learning and memory processes together with recent insight into the mechanisms mediating placebo responses provides fascinating perspectives to exploit these learned immune and neuroendocrine responses as supportive therapies, the aim being to reduce the amount of medication required, diminishing unwanted drug side effects while maximizing the therapeutic effect for the patient's benefit.

Learned Immunosuppression: Extinction, Renewal, and the Challenge of Reconsolidation

This work established a model of behaviorally conditioned immunosuppression employing a conditioned taste aversion (CTA) paradigm in the rat pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the Immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US).



Insular Cortex Lesions Impair the Acquisition of Conditioned Immunosuppression

Results show that the insular cortex is essential for the acquisition of conditioned immunosuppression, and NMDA-induced lesions did not affect the normal immune response, showing normal hemagglutinating titers and IgM production when compared to nonconditioned controls.

Differential Effects of NMDA-Induced Lesions into the Insular Cortex and Amygdala on the Acquisition and Evocation of Conditioned Immunosuppression

The results of this work suggest that the IC is involved in the neural mechanisms underlying the acquisition and evocation of conditioned immunosuppression, and the amygdala could be important in mediating the input of the immune information necessary for the acquisition of conditioned immunity.

Lesions of the hippocampus enhance or depress humoral immunity in rats.

The results suggest that different areas of the hippocampus can stimulate or inhibit humoral immunity, and chemical destruction of pyramidal cell bodies in CA2 and CA3 significantly increased humoral immune as measured by HC50, but larger chemical lesions that also included CA1 did not.

Enhancement of Antibody Production by a Learning Paradigm

The experiments described here show that production of serum antibody to a defined protein antigen can be elicited by classical Pavlovian conditioning in Wistar rats, demonstrating that the immune system can be stimulated to produce apparently normal antibody responses by a simple behavioral paradigm.

Cortical substrates of taste aversion learning: involvement of dorsolateral amygdaloid nuclei and temporal neocortex in taste aversion learning.

Results indicate that destruction of the dorsolateral amygdaloid nuclei and/or the temporal neocortices may produce CTA learning deficits by affecting olfactory, gustatory, and/ or gastrointestinal processing in various portions of the forebrain.

Conditioned Enhancement of Antibody Production Using Antigen as the Unconditioned Stimulus

A classically conditioned enhancement of anti-KLH antibody titers was observed when conditioned mice were reexposed to the CS in the context of reexposure to a minimally immunogenic dose of that same antigen.

Neuroanatomical and Functional Specificity of the Basolateral Amygdaloid Nucleus in Taste-Potentiated Odor Aversion

The results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA, and the efficacy of microinjections of a GABAA agonist into the ABL after the presentation of the odor-taste stimulus suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for T POA.

Behaviorally Conditioned Immunosuppression

Conditioned animals exposed to saccharin at the time of or following the injection of antigen were significantly immunosuppressed, and hemagglutinating antibody titers measured 6 days after antigen administration were high in placebo‐treated rats.