Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

Anagnostaras, Stephan; Maren, Stephen; Sage, Jennifer R; Goodrich, Stacy; Fanselow, Michael S.

doi:10.1016/s0893-133x(99)00083-4

Cited by 135 publications

(160 citation statements)

References 55 publications

(78 reference statements)

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“…This suggests that amphetamine is probably acting somewhere other than the hippocampus, which plays a selective role in contextual fear (Anagnostaras et al 1999a). For example, scopolamine produced a selective deficit in contextual fear consistent with anticholinergic action in the hippocampus (Anagnostaras et al 1995;Anagnostaras et al 1999b;Gale et al 2001). Previous research on moderate or high doses of amphetamine supports an interpretation of attentional deficits resulting in poor performance.…”

Section: Discussionmentioning

confidence: 90%

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

Wood

Anagnostaras

2008

Psychopharmacology

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Rationale and Objectives-With prescriptions of stimulants on the rise, it is important to examine the cognitive effects of low and moderate doses of stimulants, rather than only those typical of addicts.Methods-The present study examined the effects a range of doses (0.005 -8 mg/kg) of damphetamine sulfate on cued and contextual Pavlovian fear conditioning in mice.Results-In agreement with previous research, subjects administered a moderately high dose of amphetamine (8 mg/kg) pre-training, typical of what addicts might take, displayed impaired memory when tested, off-drug. Alternately, subjects injected with a very low dose of amphetamine (0.005, 0.025, or 0.05 mg/kg), pre-training, similar to the therapeutic doses for attention deficit hyperactivity disorder, displayed enhanced memory when tested, off-drug. A control study showed these effects were not due to state-dependent learning.Conclusions-Thus, dose is a critical determinant of the cognitive effects of psychostimulants.

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Section: Discussionmentioning

confidence: 90%

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

Wood

Anagnostaras

2008

Psychopharmacology

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“…Drug doses and injection-to-test intervals are comparable to those used in previous studies (Anagnostaras et al, 1999;Levin et al, 2000;Mendez et al, 2012;Rodgers, 1979) and were selected to minimize nonspecific motor effects.…”

Section: Drugsmentioning

confidence: 99%

Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

Ostlund¹,

Kosheleff²,

Maidment³

2013

Neuropsychopharmacol

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Reward-seeking actions can be guided by external cues that signal reward availability. For instance, when confronted with a stimulus that signals sugar, rats will prefer an action that produces sugar over a second action that produces grain pellets. Action selection is also sensitive to changes in the incentive value of potential rewards. Thus, rats that have been prefed a large meal of sucrose will prefer a grain-seeking action to a sucrose-seeking action. The current study investigated the dependence of these different aspects of action selection on cholinergic transmission. Hungry rats were given differential training with two unique stimulus-outcome (S1-O1 and S2-O2) and action-outcome (A1-O1 and A2-O2) contingencies during separate training phases. Rats were then given a series of Pavlovian-toinstrumental transfer tests, an assay of cue-triggered responding. Before each test, rats were injected with scopolamine (0, 0.03, or 0.1 mg/kg, intraperitoneally), a muscarinic receptor antagonist, or mecamylamine (0, 0.75, or 2.25 mg/kg, intraperitoneally), a nicotinic receptor antagonist. Although the reward-paired cues were capable of biasing action selection when rats were tested off-drug, both anticholinergic treatments were effective in disrupting this effect. During a subsequent round of outcome devaluation testing-used to assess the sensitivity of action selection to a change in reward value-we found no effect of either scopolamine or mecamylamine. These results reveal that cholinergic signaling at both muscarinic and nicotinic receptors mediates action selection based on Pavlovian reward expectations, but is not critical for flexibly selecting actions using current reward values.

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“…During conditioning sessions, some unconditioned behaviors were also assessed. The video images were watched in order to assess whether all infusion groups reacted to the shock by similar vigorous twitching or jumping, marked components of the unconditioned immediate shock response (Anagnostaras et al, 1999b). Activity before the first tone or shock was assessed using the percentage of changed pixels between adjacent 1-s video images that was given by the automated system.…”

Section: Basic Experimental Design Behavioral Measures and Data Anamentioning

confidence: 99%

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

2003

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ABSTRACT:Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning has been attributed to mechanisms mediated by dorsal hippocampal N-methyl-D-aspartate (NMDA)-type glutamate receptors. The present study characterized the effects of blockade or tonic stimulation of dorsal hippocampal NMDA receptors by bilateral local infusion of the noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate; 6.25 g/side) or of NMDA (0.7 g/side), respectively, on classical fear conditioning to tone and context in Wistar rats. Freezing was used to measure conditioned fear. Regardless of whether conditioning was conducted with tone-shock pairings or unsignaled footshocks (background or foreground contextual conditioning), both NMDA and MK-801 infusion before conditioning resulted in reduced freezing during subsequent exposure to the conditioning context. Freezing during subsequent tone presentation in a new context, normally resulting from conditioning with tone-shock pairings, was not impaired by MK-801 but was strongly reduced by NMDA infusion before conditioning; this freezing was also reduced by NMDA infusion before tone presentation (in an experiment involving NMDA infusions before conditioning and subsequent tone presentation to assess the role of state-dependent learning). It was assessed whether unspecific infusion effects (altered sensorimotor functions, state dependency) or infusion-induced dorsal hippocampal damage contributed to the observed reductions in conditioned freezing. Our data suggest that formation of fear conditioning to context, but not tone, requires NMDA receptor-mediated mechanisms in the dorsal hippocampus. As indicated by the effects of NMDA, some dorsal hippocampal processes may also contribute to fear conditioning to tone. The role of the dorsal hippocampus and local NMDA receptor-mediated processes in fear conditioning to tone and context is discussed in comparison with ventral hippocampal processes.

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Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

Abstract: Muscarinic-cholinergic antagonism produces learning and memory deficits in a wide

Cited by 135 publications

References 55 publications

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

Memory and psychostimulants: modulation of Pavlovian fear conditioning by amphetamine in C57BL/6 mice

Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA‐receptor blockade and stimulation

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