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


CONCLUSIONS
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.
Carnicella
Sebastien
S
Inserm U405, Strasbourg, France.
Pain
Laure
L
Oberling
Philippe
P
D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001285:Atropine / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D007274:Injections, Intraperitoneal; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D017777:Parasympathetic Fibers, Postganglionic / Q000187:drug effects / Q000502:physiology*; D010830:Physostigmine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011600:Psychopharmacology / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D018727:Muscarinic Antagonists; D001285:Atropine; D010830:Physostigmine