Nociception and Conditioned Fear in Rats: Strains Matter

Abstract

When using rats in pain research, strain-related differences in outcomes of tests for pain and nociception are acknowledged. However, very little is known about the specific characteristics of these strain differences. In this study four phylogenetically distant inbred rat strains, i.e. Wistar Kyoto (WKY), Fawn Hooded (FH), Brown Norway (BN) and Lewis (LE), were investigated in different tests related to pain and nociception. During Pavlovian fear conditioning, the LE and WKY showed a significantly longer duration of freezing behaviour than the FH and BN. Additionally, differences in c-Fos expression in subregions of the prefrontal cortex and amygdala between rat strains during retrieval and expression of conditioned fear were found. For example, the BN did not show recruitment of the basolateral amygdala, whereas the WKY, FH and LE did. During the hot plate test, the WKY and LE showed a lower thermal threshold compared to the BN and FH. In a follow-up experiment, the two most contrasting strains regarding behaviour during the hot plate test and Pavlovian fear conditioning (i.e. FH and WKY) were selected and the hot plate test, Von Frey test and somatosensory-evoked potential (SEP) were investigated. During the Von Frey test, the WKY showed a lower mechanical threshold compared to the FH. When measuring the SEP, the FH appeared to be less reactive to increasing stimulus intensities when considering both peak amplitudes and latencies. Altogether, the combined results indicate various differences between rat strains in Pavlovian fear conditioning, nociception related behaviours and nociceptive processing. These findings demonstrate the necessity of using multiple rat strains when using tests including noxious stimuli and suggest that the choice of rat strains should be considered. When selecting a strain for a particular study it should be considered how this strain behaves during the tests used in that study.

Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

“…Observations made were reported both for transparency and to identify variability factors in burrowing behaviour meriting future study. Although strain differences have been reported for other outcome measures, 8 , 42 , 63 in this study, no strain differences between Sprague-Dawley and Wistar rats were observed for suppressed burrowing. Animals with a lower body weight developed an increased burrowing deficit, whereas burrowing in sham or naive groups was unaffected.…”

Dopaminergic neurotransmission in ventral and dorsal striatum differentially modulates alcohol reinforcement

“…Cannulas were fixed to the skull using stainless steel screws and antibiotic cement (Simplex ™ P bone cement with tobramycin, Stryker Nederland B.V., The Netherlands). Anaesthesia and analgesia protocols were as previously published (Schaap et al ., , ). Briefly, rats were anaesthetized with fentanyl (0.25 mg/kg, IP – Fentanyl Janssen ® ; Janssen‐Cilag B.V., The Netherlands) and dexmedetomidine (0.15 mg/kg, IP – Dexdomitor ® ; Pfizer Animal Health B.V., The Netherlands) in their home cage.…”

Sexually Dimorphic Risk Mitigation Strategies in Rats

“…Compounding these limitations, there is a lack of representation of female animals in fear and anxiety research, caused in part by the perceived difficulty and cost in controlling the variability associated with female animals’ reproductive cycles ( Zucker and Beery, 2010 ; Prendergast et al, 2014 ; Becker et al, 2016 ). The estrous cycle of a female rat, which is typically divided into four primary “stages” (proestrus, estrus, metestrus, and diestrus), has been linked to physiological fluctuations in synapse density in the hippocampus, amygdala, and prefrontal cortex ( Woolley and McEwen, 1992 ; Shansky et al, 2004 ; Rasia-Filho et al, 2012 ), neurogenesis in the hippocampus ( Pawluski et al, 2009 ), and behavioral variation in elevated plus-maze ( Marcondes et al, 2001 ), open field ( Frye and Walf, 2002 ), fear conditioning ( Markus and Zecevic, 1997 ; Gupta et al, 2001 ), and fear extinction tests ( Milad et al, 2009 ). Completely controlling for such fluctuations systematically would require testing animals in all test stage–estrous phase combinations, demanding greater animal numbers and substantially increasing costs.…”