Repeated microinjections into the medial prefrontal cortex (mPFC) impair extinction of conditioned place preference in mice

Groblewski, Cunningham · Behavioural Brain Research · 2012 · neuroscience · 10.1016/j.bbr.2012.01.059 · record Groblewski2012-repeated-microinjections-into-the-medial-pre
tag layer · index · concepts · authors · עברית
Where this record's text came from. faceted 2026-08 by reading the locally held text (xml); every evidence string verified as an exact substring of that text before merging. Claim type is 'null-result' for the intended comparison (bupivacaine did not differ from vehicle; neither group extinguished), but the paper is equally a methodological critique: its closing claim is that the microinjection procedure as performed is unsuitable for this paradigm, which is recorded under limitations rather than duplicated as the claim shape. Replication status is 'untested' in the sense of independent replication; the paper does report internal reproduction, stating that 'the results of Experiment 2 are similar to those in Experiment 1' and that an extended replicate of Experiment 1 with six days of extinction gave the same persistent CPP. Roughly a quarter of subjects were excluded a priori as non-learners or on histological criteria, which the paper states but does not frame as a limitation of its own conclusions. 2026-08-12 and 2026-08-15 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.
6 quotations on this page contain a reference number where the paper printed a superscript. This journal style prints citations as raised numerals — parameters12,13 — and the extraction flattened them into the line, so the sentence reads parameters 12 , 13 . The digits are citation markers and not part of what the author wrote. The quotes keep them for the same reason they keep every other extraction fault: a quote is reproduced exactly or it proves nothing.
How to read this page. The article itself is not reproduced here — this paper is not cleared for redistribution, so what follows is the tag layer alone. The evidence sentences are withheld with the article. The table at the foot lists every tag the record carries; each row names the facet it belongs to, and the whose words column says whether the tag records the paper's own wording or the tagger's sentence about the paper. Every tag links to each other paper in the corpus carrying it. The machine-readable edition of the same thing is the TEI file beside this one, where the tags live in standOff, and the article is at its publisher via the link below. When we have changed our mind. Some entries in the table begin with a word in capitals and the reason for it. EVIDENCE CORRECTED — the finding still stands, but we had quoted the wrong sentence from the paper, and the quotation has been replaced with the right one. RETRACTED — the entry itself was wrong; it stays on the page, marked, with the reason, rather than being deleted. WITHDRAWN AND REPLACED — the entry was wrong, and a corrected version of it appears in the entries below. Each mark carries its own reason, in brackets, because the reasons differ from one entry to the next. An entry we have WITHDRAWN is removed from this page and kept in the record, with its reason. A line reading Audit and a date is a later re-reading of the entry against its whole sentence: DOUBTFUL means it was kept, and the reason says what is loose about it. Quotation marks inside the tagger's sentence. Where a tag is the tagger's own sentence, a phrase in quotation marks inside it is borrowed from the paper — the tagger's wording around it is not. The paper's own sentence is the evidence quote for that row; on this page it is withheld with the article, and the article is at its publisher. Nothing inside quotation marks anywhere on this page is ours: if it is quoted, it is the paper's. Whose words a concept carries. A concept entry records a term the paper itself uses, so the term, the sense given for it, and its evidence are the paper's own words, quoted where the paper fixes them. This is the opposite of a sense entry in the tag table, which is the tagger's sentence about how the paper uses a term. Where a concept entry could not be grounded in the paper's words, the entry says so on its own row.

Tags on this paper

Every tag the record carries, each linking to every other paper in the corpus that carries it. A tag appears here whether or not its words occur in the article — the spans below are only the ones a sentence in this paper licenses. Of the 16 concept tags on this paper, none is grounded in a quoted sentence. All carry the tagger's gloss of what the term means in this paper, which is not something the article can license.
medial prefrontal cortex conditioned place preference extinction bupivacaine microinjection vehicle No Sx prelimbic infralimbic guide cannula lesion nucleus accumbens basolateral amygdala complex conditioned stimuli histological criteria conditioned fear repeated cannula and injector insertion destroys tissue in Layers I-III of the mPFC on both sides of the midline, removing projection neurons that normally regulate the nucleus accumbens and basolateral amygdala, and the loss of that top-down regulation is what blocks extinction learning cumulative mechanical damage from implantation plus repeated infusions amounts to a partial lesion of a region already shown to be necessary for extinction, so the injection itself reproduces the lesion effect regardless of what is infused No Sx group injector-tip location ANOVA analysis of variance (ANOVA) two-way ANOVA with interaction term paired t-test paired t-tests Bonferroni correction for multiple comparisons Bonferroni-adjusted within-subjects comparisons alpha level / significance threshold standard error of the mean mean (± SEM) behavioural-experiment

Legend

relation to other workclaim_relationshow this paper stands to another: agrees, contradicts, extends, qualifies
claim typeclaim_typethe shape of the claim: existence, mechanism, method, critique, prediction, null
concept edgeconcept_edgesan asserted relation between two concepts, with the sentence asserting it
content tagcontent_tagsa finding, definition, quantity, statistic or variable named in the paper
controlcontrolsan experiment run to eliminate a rival explanation
limitationlimitationswhat the paper says its evidence cannot support
mechanismmechanismshow the reported effect is said to come about
methodmethodhow the paper produced its evidence
object of studyobject_of_studywhat the paper is about — the thing it investigates
phenomenonphenomenonthe effect or regularity under study
sensesensesa distinct use of a term, quoted where the paper fixes it

The paper

The full text is not reproduced here. This article is not cleared for redistribution, so the page carries the tag layer only. Its evidence sentences are withheld; the grounding status remains with each tag, and the article itself is at https://doi.org/10.1016/j.bbr.2012.01.059. The reading view exists for the papers whose licence permits it.

Every tag on this page

claim_relations 4 · claim_type 1 · concept_edges 9 · content_tags 37 · controls 1 · limitations 9 · mechanisms 8 · method 1 · object_of_study 1 · phenomenon 1 · senses 6

Relations on this page carry a quotation for the claim. Where a relation was separately evidenced — and so tested against the vocabulary for its type — the row says so; none of 9 relations here carry that mark. The rest are the tagger’s reading of the sentence quoted beside them.

facettagfieldconf.whose words
object_of_studyThe intra-mPFC microinjection procedure itself, and whether repeating it is compatible with studying extinction learning.
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object_of_studythe paper's words
claim_typenull-result
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claim_typethe paper's words
phenomenonextinction of ethanol-induced conditioned place preference
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phenomenonthe paper's words
methodbehavioural-experiment
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methodthe paper's words
mechanismsmechanisms
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mechanisms[0]the tagger's words
mechanismsmechanisms
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mechanisms[1]the tagger's words
mechanismsThe vehicle group could not serve as the control, because whatever impaired extinction affected vehicle and drug alike
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mechanisms[2]the tagger's words
mechanismsOnly a group that never had the procedure could reveal it, which is why the no-surgery control was added in the second experiment
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mechanisms[3]the tagger's words
mechanismsThe proposed cause: the repeated procedure damages the very region it is delivering into, amounting to a partial lesion
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mechanisms[4]the tagger's words
mechanismsBecause the cannula sat on the midline, the damage was bilateral rather than confined to one hemisphere
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mechanisms[5]the tagger's words
mechanismsThe damaged layers contain projection neurons to accumbens and amygdala whose activity changes with drug cues, which is a route from local damage to the behavioural failure
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mechanisms[6]the tagger's words
mechanismsSurgery and anaesthesia were ruled out by comparison with their own earlier study matched on strain, frame, coordinates, anaesthesia and surgeon
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mechanisms[7]the tagger's words
limitationsThe planned within-subject comparisons were run regardless of the interaction and are acknowledged as not statistically justified.
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what this limits: every within-subject comparison reported: THIS METHOD OF ANALYSIS, ALTHOUGH NOT STATISTICALLY JUSTIFIED, WAS IMPLEMENTED BECAUSE OF THE NARROW DETECTION WINDOW AND INCREASED VARIABILITY inherent to the paradigm
limitations[0]the tagger's words
limitationsThe proposed explanation via damage to mPFC projection neurons is untested and needs confirmation.
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what this limits: the projection-damage explanation: FURTHER EXAMINATION OF THE EFFECTS OF THE MICROINJECTION PROCEDURE ON THESE SPECIFIC PROJECTIONS ... IS REQUIRED - proposed, not tested
limitations[1]the tagger's words
limitationsAs performed, the microinjection procedure cannot be used to test intra-mPFC pharmacological manipulations of EtOH-CPP extinction.
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what this limits: any pharmacological use of this procedure: IRRESPECTIVE OF HOW EACH COMPONENT ... CONTRIBUTES TO THE OBSERVED EFFECT, AS CURRENTLY PERFORMED, THIS PROCEDURE IS NOT ADEQUATELY SUITED TO EXAMINE THE EFFECTS OF INTRA-mPFC PHARMACOLOGICAL MANIPULATIONS ON EXTINCTION
limitations[2]the tagger's words
limitationsThe authors state that their own analysis is not statistically justified, and say why they used it anyway
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duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - the within-subject comparisons are acknowledged as not statistically justified, with the reason given
limitations[3]the tagger's words
limitationsAnimals were removed for failing to acquire a preference and for histology, about a third of each experiment
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what this limits: the sample behind Experiment 1: A TOTAL OF 18 ANIMALS WERE REMOVED FROM ANALYSIS (9 SHOWED LESS THAN 50% PREFERENCE ON TEST 1 AND AN ADDITIONAL 9 WERE REMOVED FOR NOT MEETING HISTOLOGICAL CRITERIA)
limitations[4]the tagger's words
limitationsNon-learners were excluded by an a priori rule, which is disclosed and defended by reference to prior practice
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what this limits: the same scope as limitations[4], with the rule and its justification: WE DECIDED, A PRIORI, TO REMOVE ANIMALS THAT FAILED TO EXPRESS A PLACE PREFERENCE OF GREATER THAN 50% ON TEST 1
limitations[5]the tagger's words
limitationsThe strongest extra evidence - doubling extinction to six days - is reported as data not shown
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what this limits: the strongest supporting evidence for the extinction claim, which is not shown: DESPITE DOUBLING THE NUMBER OF EXTINCTION TRIALS, WE FOUND THAT BOTH mPFC-INJECTED GROUPS CONTINUED TO EXHIBIT IMPAIRED EXTINCTION
limitations[6]the tagger's words
limitationsThe damage-to-projection account is offered as conceivable and explicitly not established
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what this limits: the same scope as limitations[1] - the damage-to-projection account is offered as conceivable and explicitly not established
limitations[7]the tagger's words
limitationsNo group-by-test interaction reached significance in either experiment, so the key contrast rests on the planned within-group comparisons
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what this limits: the central group contrast: THE INITIAL 2-WAY ANOVA REVEALED A MAIN EFFECT OF TEST [F(1,40) = 9.3, p < .005] BUT NOT GROUP, AND NO SIGNIFICANT GROUP x TEST INTERACTION (p's > .05), so the effect rests on the planned comparisons
limitations[8]the tagger's words
controlsan additional group given NO SURGERY AT ALL (the No Sx group), alongside the vehicle-infused and drug-infused groups
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eliminates: the handling involved in the microinjection procedure - being restrained and manipulated - as the cause of the change in extinction learning, which a vehicle control alone cannot separate because it is handled too · outcome (stated by the tagger, no quotation): held
controls[0]0.95the tagger's words
sensescontrol - VEHICLE: everything but the drug, which is the standard control and here shares the confound
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senses[0]1.0the tagger's words
sensescontrol - NO PROCEDURE AT ALL: no surgery, no cannula, no injection, and the only group in which extinction occurred
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senses[1]1.0the tagger's words
sensesthe manipulation - as intended: reversible pharmacological inactivation of a region during extinction trials
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senses[2]1.0the tagger's words
sensesthe manipulation - as delivered: cumulative mechanical damage from repeating the delivery, which is a lesion and not an inactivation
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senses[3]1.0the tagger's words
sensesextinction procedure - single-session, as in conditioned fear, where one injection suffices and this problem never arises
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senses[4]the tagger's words
sensesextinction procedure - multi-day, as required for ethanol place preference, where the injections must be repeated and the damage accumulates
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senses[5]1.0the tagger's words
claim_relationsextends → Groblewski et al. mPFC lesion findings [1] and the rat bupivacaine microinjection procedure [2]
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claim_relations[0]the tagger's words
claim_relationsbuilds-on → Groblewski et al. (2011) [1] electrode-insertion control result
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claim_relations[1]the tagger's words
claim_relationsextends → Groblewski et al. on mPFC lesions impairing extinction of ethanol place preference
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claim_relations[2]the tagger's words
claim_relationscritiques → the repeated intra-mPFC microinjection procedure as a tool for multi-day extinction studies
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differs in: THE AXIS IS THE NUMBER OF INJECTIONS, AND MINIMISING IT DOES NOT HELP. 'the damage caused by intra-mPFC injections even when the number of injections was minimized, was sufficient enough to impair extinction - an effect that persisted despite extended extinction training.' The critique of the procedure is dosed: it survives the obvious remedy.
claim_relations[3]the tagger's words
concept_edgesmicroinjection —causes→ lesion
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strength of the relation: 0.9 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the tissue damage 'MAY HAVE BEEN sufficient' to amount to a lesion; causes is hedged.
concept_edges[0]the tagger's words
concept_edgesmicroinjection —causes→ extinction
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strength of the relation: 1
concept_edges[1]the tagger's words
concept_edgesmedial prefrontal cortex —causes→ extinction
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strength of the relation: 1
concept_edges[2]the tagger's words
concept_edgesEVIDENCE CORRECTED (RE-GROUNDED) · vehicle —contrasted-with→ No Sx
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EVIDENCE CORRECTED: RE-GROUNDED. The old span named only the No Sx group. This sentence names both and carries the contrast with its direction - 'the No Sx, BUT NOT Vehicle or Bupivacaine, group…'. — strength of the relation: 1
also in: vehicle · No Sx
concept_edges[3]the tagger's words
concept_edgesprelimbic —part-of→ medial prefrontal cortex
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strength of the relation: 1
concept_edges[5]the tagger's words
concept_edgesinfralimbic —part-of→ medial prefrontal cortex
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strength of the relation: 1
concept_edges[6]the tagger's words
concept_edgesguide cannula —part-of→ microinjection
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strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but a guide cannula was IMPLANTED for the microinjections; part-of is loose.
concept_edges[7]the tagger's words
concept_edgesconditioned place preference —operationalised-as→ conditioned stimuli
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strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the conditioned stimuli were the tactile cues of the place-preference task; operationalised-as is loose.
concept_edges[9]the tagger's words
concept_edgesconditioned fear —contrasted-with→ conditioned place preference
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differs in: THE AXIS IS HOW MUCH TRAINING EXTINCTION TAKES. 'Quotation withheld' Both are extinction; they differ on the schedule needed, which is why a procedure validated on one can fail on the other for reasons that have nothing to do with the mechanism. · strength of the relation: 1
concept_edges[10]the tagger's words
content_tagsANOVA
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also in: ANOVA
content_tags.statistics[0]the tagger's words
content_tagstwo-way ANOVA with interaction term
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content_tags.statistics[1]the tagger's words
content_tagspaired t-test
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also in: paired t-test
content_tags.statistics[2]the tagger's words
content_tagsBonferroni correction for multiple comparisons
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content_tags.statistics[3]the tagger's words
content_tagsalpha level / significance threshold
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content_tags.statistics[4]the tagger's words
content_tagsstandard error of the mean
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content_tags.statistics[5]the tagger's words
content_tagsNeither the vehicle nor the bupivacaine group showed significant extinction of ethanol place preference.
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content_tags.findings[0]the tagger's words
content_tagsIn the second experiment only the no-surgery group showed a significant drop in place preference.
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content_tags.findings[1]the tagger's words
content_tagsThe experiments suggest some component of the microinjection procedure, not merely the handling, interfered with extinction.
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content_tags.findings[2]the tagger's words
content_tagsDoubling the extinction trials did not rescue extinction: both injected groups kept showing place preference.
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content_tags.findings[3]the tagger's words
content_tagsThe authors conclude the repeated intra-mPFC microinjection technique, as performed, is unsuitable for studying extinction of ethanol place preference in mice.
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content_tags.findings[4]the tagger's words
content_tagsSurgery and anaesthesia alone are ruled out as the cause, since a single electrode insertion at the same coordinates in earlier work left extinction intact.
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content_tags.findings[5]the tagger's words
content_tagsvehicle and bupivacaine groups both failed to extinguish
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content_tags.findings[6]the tagger's words
content_tagsin the second experiment only the unoperated group extinguished
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content_tags.findings[7]the tagger's words
content_tagshandling alone does not explain it, since the no-surgery group was handled and still extinguished
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content_tags.findings[8]the tagger's words
content_tagsthe tissue damage was substantial and limited mainly to layers I-III of the mPFC
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content_tags.findings[9]the tagger's words
content_tagsdoubling the extinction training did not rescue it
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content_tags.findings[10]the tagger's words
content_tagssurgery and anaesthesia were ruled out by a matched earlier study in which a single electrode insertion did not impair extinction
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content_tags.findings[11]the tagger's words
content_tagsbupivacaine
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also in: bupivacaine
content_tags.definitions[1]the tagger's words
content_tagsbupivacaine
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also in: bupivacaine
content_tags.definitions[2]the tagger's words
content_tagsextinction
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also in: extinction
content_tags.definitions[3]the tagger's words
content_tagsNo Sx group
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also in: No Sx group
content_tags.variables[3]the tagger's words
content_tagsinjector-tip location
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content_tags.variables[9]the tagger's words
content_tagsn=108 — total number of adult male DBA/2J mice used across the experiments
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content_tags.quantities[0]the tagger's words
content_tagsF (1,33) = 4.3, p < .05 — main effect of Test on percent time on the ethanol-paired floor in Experiment 1
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content_tags.quantities[1]the tagger's words
content_tagsF (1,40) = 9.3, p < .005 — main effect of Test on place preference in Experiment 2
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content_tags.quantities[2]the tagger's words
content_tagst (11) = 2.5 p < .05 — the only significant within-group preference reduction, found in the No-Surgery group
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content_tags.quantities[3]the tagger's words
content_tags18 — animals excluded from Experiment 1, split between failure to show preference and failed histology
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content_tags.quantities[4]the tagger's words
content_tagsless than 25% — share of subjects that failed to acquire a place preference after two conditioning trials
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content_tags.quantities[5]the tagger's words
content_tags.05 — the alpha level adopted for all statistical tests
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content_tags.quantities[6]the tagger's words
content_tags0.2 μL over 2 min (0.1 μL/min) — volume and rate of each intra-mPFC infusion of vehicle or bupivacaine
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content_tags.quantities[7]the tagger's words
content_tagsn=108 — total mice across both experiments before exclusions
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content_tags.quantities[8]the tagger's words
content_tags18 animals removed — exclusions in Experiment 1 - nine non-learners and nine on histology
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content_tags.quantities[9]the tagger's words
content_tags16 animals removed — the equivalent in Experiment 2
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content_tags.quantities[10]the tagger's words
content_tags0.2 μL over 2 min — the injection volume and rate, chosen to inactivate most of the target subregions
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content_tags.quantities[11]the tagger's words
content_tags>90% of neuronal activation — the intended coverage of the inactivation, from prior diffusion studies
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content_tags.quantities[12]the tagger's words
content_tags2 g/kg — the ethanol dose paired with the floor cue
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content_tags.quantities[13]the tagger's words

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