Skip to main content
SpringerLink
Log in

Cholinergic effects on fear conditioning I: the degraded contingency effect is disrupted by atropine but reinstated by physostigmine

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

The cholinergic system has been shown to modulate contextual fear conditioning. However, with the exception of trace conditioning studies, most of the available data have focussed on independent context, i.e., context that do not compete with the conditioned stimulus to control for the conditioned response (interactive context).

Objective

In the present series of experiments, the effects of the muscarinic antagonist, atropine, were assessed when contextual fear memory interacts with cued fear memory to regulate conditioned response, using a Pavlovian degraded contingency preparation in rats. This preparation not only afforded an insight into simple Pavlovian associations but also enabled us to test for the processes of competition that made use of these associations to make an appropriate response to a stimulus [degraded contingency effect (DCE)].

Methods

In experiment 1, three doses of atropine [2.5, 5.0, and 10.0 mg/kg, intraperitoneally (i.p.)] were evaluated on male Sprague–Dawley rats. In experiment 2, physostigmine (0.037–0.3 mg/kg, i.p.) was injected after the administration of 5 mg/kg of atropine.

Results

Experiment 1A and its partial replication (experiment 1B) showed that at asymptotic level of training, atropine did not alter contextual and cued fear memories when the subjects were directly tested for them, whereas it suppressed the DCE for a 5 mg/kg dose. Indeed, atropine-induced suppression of the DCE was found to be an inverted U-shaped dose–response curve. Experiment 2 showed that physostigmine caused a dose-dependent reversal of the atropine-induced alleviation of the DCE, without altering the expression of simple cued and contextual fear memories.

Conclusion

These results evidence at asymptotic level of training a cholinergic modulation of the processing of interactive context, but not of independent ones. They are discussed in the framework of the mechanisms that are involved in both types of contextual processing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Anagnostaras SG, Maren S, Fanselow MS (1995) Scopolamine selectively disrupts the acquisition of contextual fear conditioning in rats. Neurobiol Learn Mem 64:191–194

    Article  Google Scholar 

  • Anagnostaras SG, Maren S, Sage JR, Goodrich S, Fanselow MS (1999) Scopolamine and Pavlovian fear conditioning in rats: dose–effect analysis. Neuropsychopharmacology 21:731–744

    Article  Google Scholar 

  • Baddeley AD (1982) Domains of recollection. Psychol Rev 89:708–729

    Article  Google Scholar 

  • Bazin N, Hardy-Bayle MC, Perruchet P, Feline A (2000) Context-dependent information processing in patients with schizophrenia. Schizophr Res 45:93–101

    Article  Google Scholar 

  • Bouton ME (1993) Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol Bull 114:80–99

    Article  Google Scholar 

  • Bouton ME, Peck CA (1989) Context effects on conditioning, extinction, and reinstatement in an appetitive conditioning preparation. Anim Learn Behav 17:188–198

    Google Scholar 

  • Caulfield MP, Birdsall NJ (1998) International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol Rev 50:279–290

    CAS  PubMed  Google Scholar 

  • Christian KM, Thompson RF (2003) Neural substrates of eyeblink conditioning: acquisition and retention. Learn Mem 10:427–455

    Article  PubMed  Google Scholar 

  • Cohen JD, Servan-Schreiber D (1992) Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia. Psychol Rev 99:45–77

    Article  CAS  PubMed  Google Scholar 

  • Cole RP, Barnet RC, Miller RR (1995) Temporal encoding in trace conditioning. Anim Learn Behav 23:144–153

    Google Scholar 

  • Disterhoft JF, Oh MM (2003) Modulation of cholinergic transmission enhances excitability of hippocampal pyramidal neurons and ameliorates learning impairments in aging animals. Neurobiol Learn Mem 80:223–233

    Article  Google Scholar 

  • Disterhoft JF, Kronforst-Collins M, Oh MM, Power JM, Preston AR, Weiss C (1999) Cholinergic facilitation of trace eyeblink conditioning in aging rabbits. Life Sci 64:541–548

    Article  Google Scholar 

  • Dixon WJ (1988) BMDP statistical manual. University of California Press, Berkeley

    Google Scholar 

  • Dumery V, Derer P, Blozovski D (1988) Enhancement of passive avoidance learning through small doses of intra-amygdaloid physostigmine in the young rat. Its relation to the development of acetylcholinesterase. Dev Psychobiol 21:553–565

    Article  Google Scholar 

  • Durlach PJ (1983) Effect of signaling intertrial unconditioned stimuli in autoshaping. J Exp Psychol Anim Behav Process 9:374–389

    Article  Google Scholar 

  • Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48:649–684

    Article  CAS  PubMed  Google Scholar 

  • Gallistel CR, Gibbon J (2000) Time, rate, and conditioning. Psychol Rev 107:289–344

    Article  Google Scholar 

  • Gibbon J (1977) Scalar expectancy theory and Weber’s law in animal timing. Psychol Rev 84:279–325

    Article  Google Scholar 

  • Gibbon J, Balsam P (1981) Spreading association in time. In: Locurto CM, Terrace HS, Gibbon J (eds) Autoshaping and conditioning theory. Academic Press, New York, pp 219–253

    Google Scholar 

  • Gibbon J, Church RM, Meck WH (1984) Scalar timing in memory. In: Gibbon J, Allan LG (eds) Timing and time perception. Ann N Y Acad Sci 423:52–77

    CAS  PubMed  Google Scholar 

  • Gold PE (2003) Acetylcholine modulation of neural systems involved in learning and memory. Neurobiol Learn Mem 80:194–210

    Article  Google Scholar 

  • Hall G, Honey RC (1990) Context-specific conditioning in the conditioned-emotional-response procedure. J Exp Psychol Anim Behav Process 16:271–278

    Article  Google Scholar 

  • Kasprow WJ, Schachtman TR, Miller RR (1987) The comparator hypothesis of conditioned response generation: manifest conditioned excitation and inhibition as a function of relative excitatory strengths of CS and conditioning context at the time of testing. J Exp Psychol Anim Behav Process 13:395–406

    Article  Google Scholar 

  • Kaye H, Mackintosh NJ (1990) A change of context can enhance performance of an aversive but not of an appetitive conditioned response. Q J Exp Psychol B Comp Physiol Psychol 42:113–134

    Google Scholar 

  • Keppel G (1982) Design and analysis: a researcher handbook, 2nd edn. Prentice Hall, Englewood Cliffs

    Google Scholar 

  • McAlonan GM, Wilkinson LS, Robbins TW, Everitt BJ (1995) The effects of AMPA-induced lesions of the septohippocampal cholinergic projection on aversive conditioning to explicit and contextual cues and spatial learning in the water maze. Eur J Neurosci 7:281–292

    Google Scholar 

  • Meck WH (1996) Neuropharmacology of timing and time perception. Cogn Brain Res 3:227–242

    Article  Google Scholar 

  • Meck WH, Church RM (1987) Cholinergic modulation of the content of temporal memory. Behav Neurosci 101:457–464

    Article  Google Scholar 

  • Miller RR, Barnet RC (1993) The role of time in elementary associations. Curr Dir Psychol Sci 2:106–111

    Article  Google Scholar 

  • Miller RR, Matzel LD (1989) Contingency and relative associative strength. In: Klein SB, Mowrer RR (eds) Contemporary learning theories: Pavlovian conditioning and the status of traditional learning theory. Laurence Erlbaum Associates, Hillsdale, NJ, pp 61–84

    Google Scholar 

  • Mirza NR, Stolerman IP (2000) The role of nicotinic and muscarinic acetylcholine receptors in attention. Psychopharmacology 148:243–250

    Article  CAS  PubMed  Google Scholar 

  • Myers CE, Ermita BR, Harris K, Hasselmo M, Solomon P, Gluck MA (1996) A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning. Neurobiol Learn Mem 66:51–66

    Article  Google Scholar 

  • Oberling P, Bristol AS, Matute H, Miller RR (2000) Biological significance attenuates overshadowing, relative validity, and degraded contingency effects. Anim Learn Behav 28:172–186

    Google Scholar 

  • Rescorla RA (1968) Probability of shock in the presence and absence of CS in fear conditioning. J Comp Physiol Psychol 66:1–5

    Google Scholar 

  • Rescorla RA, Wagner AR (1972) A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement. In: Black AH, Prokasy WF (eds) Classical conditioning: II. Current theory and research. Appleton-Century-Crofts, New York, pp 64–99

    Google Scholar 

  • Rudy JW (1996) Scopolamine administered before and after training impairs both contextual and auditory-cue fear conditioning. Neurobiol Learn Mem 65:73–81

    Article  Google Scholar 

  • Simon BB, Knuckley B, Powell DA (2004) Galantamine facilitates acquisition of a trace-conditioned eyeblink response in healthy, young rabbits. Learn Mem 11:116–122

    Article  Google Scholar 

  • Solomon PR, Groccia-Ellison ME, Flynn D, Mirak J, Edwards KR, Dunehew A, Stanton ME (1993) Disruption of human eyeblink conditioning after central cholinergic blockade with scopolamine. Behav Neurosci 107:271–279

    Article  Google Scholar 

  • Tinsley MR, Quinn JJ, Fanselow MS (2004) The role of muscarinic and nicotinic cholinergic neurotransmission in aversive conditioning: comparing Pavlovian fear conditioning and inhibitory avoidance. Learn Mem 11:35–42

    Article  Google Scholar 

  • Wall PM, Flinn J, Messier C (2001) Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice. Psychopharmacology 155:58–68

    Article  Google Scholar 

  • Weiss C, Preston AR, Oh MM, Disterhoft JF, Schwarz RD, Welty D (2000) The M1 muscarinic agonist CI-1017 facilitates trace eyeblink conditioning in aging rabbits and increases the excitability of CA1 pyramidal neurons. J Neurosci 20:783–790

    Google Scholar 

  • Woodruff-Pak DS, Santos IS (2000) Nicotinic modulation in an animal model of a form of associative learning impaired in Alzheimer’s disease. Behav Brain Res 113:11–19

    Article  Google Scholar 

  • Young SL, Bohenek DL, Fanselow MS (1995) Scopolamine impairs acquisition and facilitates consolidation of fear conditioning: differential effects for tone vs context conditioning. Neurobiol Learn Mem 63:174–180

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by MENRT “Action Concertée Incitative Cognitique” grant 1A019F and Fondation NRJ - Institut de France. Sebastien Carnicella was supported by a French predoctoral fellowship from the MNERT.

The authors would like to thank Justin Joffe and Ralph R. Miller for their helpful comments throughout the preparation of this manuscript, Marie-Josée Angst for her technical assistance, and Raymond Willhelm for the care he lavished on the rats. Thanks are also due to Andrew Wright for his help with the English language.

Author information

Authors and Affiliations

  1. Inserm U405, Strasbourg, France

    Sebastien Carnicella & Laure Pain

  2. ULP-CNRS UMR7521, 12 rue Goethe, 67000, Strasbourg, France

    Philippe Oberling

Authors
  1. Sebastien Carnicella
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laure Pain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philippe Oberling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philippe Oberling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carnicella, S., Pain, L. & Oberling, P. Cholinergic effects on fear conditioning I: the degraded contingency effect is disrupted by atropine but reinstated by physostigmine. Psychopharmacology 178, 524–532 (2005). https://doi.org/10.1007/s00213-005-2176-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-2176-8

Keywords

Search

Navigation