Effects of dopamine D1 modulation of the anterior cingulate cortex in a fear conditioning procedure

Abstract

The anterior cingulate cortex (AC) component of the medial prefrontal cortex (mPFC) has been implicated in attention and working memory as measured by trace conditioning. Since dopamine (DA) is a key modulator of mPFC function, the present study evaluated the role of DA receptor agents in rat AC, using trace fear conditioning. A conditioned stimulus (CS, noise) was followed by an unconditioned stimulus (US, shock) with or without a 10 s trace interval interposed between these events in a between-subjects design. Conditioned suppression of drinking was assessed in response to presentation of the CS or an experimental background stimulus (flashing lights, previously presented for the duration of the conditioning session). The selective D1 agonist SKF81297 (0.05 μg/side) or D1 antagonist SCH23390 (0.5 μg/side) was administered by intra-cerebral microinfusion directly into AC. It was predicted that either of these manipulations should be sufficient to impair trace (but not delay) conditioning. Counter to expectation, there was no effect of DA D1 modulation on trace conditioning as measured by suppression to the noise CS. However, rats infused with SKF81297 acquired stronger conditioned suppression to the experimental background stimulus than those infused with SCH23390 or saline. Thus, the DA D1 agonist SKF81297 increased conditioned suppression to the contextual background light stimulus but was otherwise without effect on fear conditioning.

The dopamine D1 receptor agonist SKF81297 has dose-related effects on locomotor activity but is without effect in a CER trace conditioning procedure conducted with two versus four trials

“…This latter effect is broadly consistent with the results seen after localised micro-infusion of SKF81297 in the anterior cingulate part of the mPFC. However, with the more localised administration and the standard two conditioning trials there was evidence for overall increased conditioning to the experimental background ( Pezze, Marshall, Domonkos, & Cassaday, 2016 ). In the present study, the observed effect was not so systematic.…”

Potentiation rather than distraction in a trace fear conditioning procedure

“…Thus, it has been argued that the use of a distractor is an important procedural modification in order to model the putative attentional role of AC in a task with demonstrated sensitivity to attentional parameters and high translational relevance to our understanding of normal human ageing. Moreover, it follows that increased attentional load may be a contributing factor in the event trace conditioning deficits are demonstrated in rodent models, at least to the extent that these depend on attentional processes mediated by the AC ( Pezze et al, 2016 ).…”

“…In a series of trace conditioning experiments using rat fear conditioning procedures, we have routinely used an extended background stimulus ( Norman and Cassaday, 2003 , Horsley and Cassaday, 2007 , Grimond-Billa et al, 2008 , Nelson et al, 2011 , Pezze et al, 2016 ). This was provided by a continuously flashing light presented for the full duration of the conditioning session and has been intended to provide an experimental context rather than a distractor stimulus.…”

“…Rather the present study sought to explore the feasibility of adapting a published distractor procedure, in order (in the longer term) to further examine the role of AC in working memory. This behavioural work was done in a rat rather than a mouse model and using a different variant of trace fear conditioning (suppression of licking rather than freezing), as per a number of earlier studies conducted to examine the neuropharmacological substrates of trace conditioning ( Norman and Cassaday, 2003 , Horsley and Cassaday, 2007 , Grimond-Billa et al, 2008 , Nelson et al, 2011 , Pezze et al, 2016 ).…”

Papel dos mecanismos GABAérgicos do colículo inferior e da substância cinzenta periaquedutal na interface sensoriomotora do medo e ansiedade

“…Usually, light is used as conditioned cue that precedes the aversive/rewarding stimulus in other protocols (Cassaday & Thur, 2015;Pezze et al, 2016). Here, we present the protocol that has been used and an initial screening of the effects of two drugs in the test: diazepam (a well-known benzodiazepine used as anxiolytic in clinical practice) and meta-Chlorophenylpiperazine (mCPP), a recreational drug with anxiogenic properties, pharmacologically classified as a non-specific agonist for serotonin receptors.…”