Neural substrates for behaviorally conditioned immunosuppression in the rat.
We have previously demonstrated behaviorally conditioned immunosuppression using cyclosporin A as an unconditioned stimulus and saccharin as a conditioned stimulus. In the current study, we examined the central processing of this phenomenon generating excitotoxic lesions before and after acquisition to discriminate between learning and memory processes. Three different brain areas were analyzed: insular cortex (IC), amygdala (Am), and ventromedial nucleus of the hypothalamus (VMH). The results demonstrate that IC lesions performed before and after acquisition disrupted the behavioral component of the conditioned response (taste aversion). In contrast, Am and VMH lesions did not affect conditioned taste aversion. The behaviorally conditioned suppression of splenocyte proliferation and cytokine production (interleukin-2 and interferon-gamma) was differentially affected by the excitotoxic lesions, showing that the IC is essential to acquire and evoke this conditioned response of the immune system. In contrast, the Am seems to mediate the input of visceral information necessary at the acquisition time, whereas the VMH appears to participate within the output pathway to the immune system necessary to evoke the behavioral conditioned immune response. The present data reveal relevant neural mechanisms underlying the learning and memory processes of behaviorally conditioned immunosuppression.
Pacheco-López
Gustavo
G
Department of Medical Psychology, University Duisburg-Essen, D-45122 Essen, Germany. gustavo.pacheco@ifv.gess.ethz.ch
Niemi
Maj-Britt
MB
Kou
Wei
W
Härting
Margarete
M
Fandrey
Joachim
J
Schedlowski
Manfred
M
D000679:Amygdala / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000139:chemically induced / Q000503:physiopathology; D001931:Brain Mapping; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D007033:Hypothalamus, Middle / Q000276:immunology / Q000502:physiology; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007958:Leukocyte Count / Q000379:methods; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013997:Time Factors
D016207:Cytokines; D007166:Immunosuppressive Agents; D016202:N-Methylaspartate; D016572:Cyclosporine
J Neurosci. 1999 Jun 1;19(11):4533-43
10341253
Life Sci. 1999;64(17):1473-83
10353612
Am J Physiol. 1999 Jun;276(6):R1710-7
10362751
Brain Behav Immun. 1999 Mar;13(1):46-60
10371677
J Neuroimmunol. 1999 Feb 1;94(1-2):172-81
10376951
Learn Mem. 1998 Nov-Dec;5(6):481-92
10489263
Brain Res. 1999 Aug 28;839(2):323-30
10519056
Behav Brain Res. 2000 Jun 1;110(1-2):129-41
10802310
Am J Physiol Regul Integr Comp Physiol. 2000 Oct;279(4):R1310-5
11003998
Auton Neurosci. 2000 Dec 20;85(1-3):49-59
11189026
Auton Neurosci. 2000 Dec 20;85(1-3):60-5
11189027
Science. 2001 Mar 23;291(5512):2417-9
11264539
J Neuroimmunol. 2001 Aug 30;118(2):245-55
11498259
Neurosci Biobehav Rev. 2001 Jul;25(5):395-407
11566478
Behav Brain Res. 2002 Apr 1;131(1-2):205-9
11844587
Annu Rev Immunol. 2002;20:125-63
11861600
J Neuroimmunol. 2002 Feb;123(1-2):102-11
11880155
Immunol Rev. 2001 Dec;184:226-35
12086315
Curr Opin Neurobiol. 2002 Aug;12(4):448-54
12139994
Q J Exp Psychol B. 2002 Jul;55(3):213-39
12188525
J Neuroimmunol. 2002 Oct;131(1-2):21-30
12458033
J Neuroimmunol. 2002 Oct;131(1-2):50-9
12458036
Nature. 2002 Dec 19-26;420(6917):853-9
12490958
J Endocrinol Invest. 2002 Nov;25(10):836-54
12508946
J Neuroimmunol. 1992 Dec;41(2):215-22
1334967
Am J Physiol. 1992 Sep;263(3 Pt 2):R544-52
1415640
Clin Investig. 1992 Sep;70(9):773-9
1450631
J Neurophysiol. 2004 Mar;91(3):1143-57
14627662
Brain Res Bull. 2004 Jan 15;62(4):271-83
14709342
Nat Rev Neurosci. 2004 Mar;5(3):209-17
14976520
Behav Brain Res. 2004 Oct 5;154(2):557-65
15313045
Brain Res. 1992 Jan 13;569(2):221-8
1540828
J Neuroimmunol. 2005 Jan;158(1-2):1-2
15589031
J Neuroimmunol. 2005 Jan;158(1-2):3-13
15589032
Brain Res. 1991 May 17;549(1):165-70
1654172
Am J Physiol. 1990 Jan;258(1 Pt 2):R245-55
2301638
Brain Res Bull. 1987 Feb;18(2):191-203
2436726
Brain Res. 1989 Mar 6;481(2):298-303
2566357
Neurosci Lett. 1989 Feb 27;97(3):252-8
2717061
Ann N Y Acad Sci. 1985;443:8-21
3860080
Behav Neurosci. 1983 Feb;97(1):110-9
6301516
Science. 1978 Jul 21;201(4352):267-9
663655
Nature. 1983 Nov 10-16;306(5939):181-4
6646199
Brain Res. 1978 Sep 15;153(1):1-26
679038
Am J Psychol. 1980 Dec;93(4):631-41
7212131
Brain Res. 1980 May 26;190(2):321-32
7370794
Endocr Res. 1995 Aug;21(3):623-33
7588431
Life Sci. 1995;57(11):1011-26
7658909
Behav Brain Res. 1994 Dec 15;65(2):123-37
7718144
Neurosci Res. 1995 Mar;22(1):31-49
7792081
Physiol Behav. 1994 Dec;56(6):1197-202
7878091
J Endocrinol. 1995 Jan;144(1):159-64
7891018
Brain Res. 1994 Jul 25;652(1):164-8
7953716
Brain Res. 1994 Apr 11;642(1-2):290-6
8032891
Behav Brain Res. 1993 Dec 31;59(1-2):11-7
8155277
Endocrinology. 1993 Dec;133(6):3054-7
8243337
Clin Pharmacokinet. 1993 Jun;24(6):472-95
8513650
J Comp Physiol Psychol. 1977 Jun;91(3):498-507
874118
Brain Behav Immun. 1996 Jun;10(2):103-14
8811934
Brain Res. 1996 Nov 11;739(1-2):308-13
8955952
Trends Neurosci. 1997 Dec;20(12):565-70
9416669
Physiol Behav. 1998 Jan;63(2):241-7
9423965
Brain Behav Immun. 1998 Jun;12(2):149-60
9646939
Am J Physiol. 1998 Aug;275(2):H689-96
9683459
J Neuroimmunol. 1998 Aug 1;88(1-2):182-91
9688340
Trends Neurosci. 1998 Aug;21(8):323-31
9720596
Transplant Proc. 1998 Aug;30(5):2033
9723379
J Comp Neurol. 1998 Oct 5;399(4):440-68
9741477
Biochem Biophys Res Commun. 1999 Jan 8;254(1):169-73
9920752