Skip to main content
main-content
Erschienen in: Brain Structure and Function 7/2021

30.06.2021 | Original Article

Repeated cocaine exposure prior to fear conditioning induces persistency of PTSD-like symptoms and enhancement of hippocampal and amygdala cell density in male rats

verfasst von: Asmae Lguensat, Christian Montanari, Cassandre Vielle, Mohamed Bennis, Saadia Ba-M’hamed, Christelle Baunez, René Garcia

Erschienen in: Brain Structure and Function | Ausgabe 7/2021

Einloggen, um Zugang zu erhalten

Abstract

Pre- and post-trauma drug use can interfere with recovery from post-traumatic stress disorder (PTSD). However, the biological underpinnings of this interference are poorly understood. Here we examined the effect of pre-fear conditioning cocaine self-administration on PTSD-like symptoms in male rats, and defined impairment of fear extinction as difficulty to recover from PTSD. We also examined cell density changes in brain regions suspected of being involved in resistance to PTSD recovery. Before footshock stress testing, rats were trained to self-administer cocaine during 20 consecutive days, after which they were exposed to footshocks, while other rats continued to self-administer cocaine until the end of the experiment. Upon assessment of three PTSD-like symptoms (fear during situational reminders, anxiety-like behavior, and impairment of recognition memory) and fear extinction learning and memory, changes in cell density were measured in the medial prefrontal cortex, hippocampus, and amygdala. Results show that pre-footshock cocaine exposure did not affect fear during situational reminders. Fear conditioning did not lead to an increase in cocaine consumption. However, in footshock stressed rats, cocaine induced a reduction of anxiety-like behavior, an aggravation of recognition memory decline, and an impairment of extinction memory. These behavioral alterations were associated with increased cell density in the hippocampal CA1, CA2, and CA3 regions and basolateral amygdala, but not in the medial prefrontal cortex. Our findings suggest that enhancement of cell density in the hippocampus and amygdala may be changes associated with drug use, interfering with PTSD recovery.
Literatur
Zurück zum Zitat Back S, Dansky BS, Coffey SF, Saladin ME, Sonne S, Brady KT (2000) Cocaine dependence with and without post-traumatic stress disorder: a comparison of substance use, trauma history and psychiatric comorbidity. Am J Addict 9(1):51–62 CrossRefPubMed Back S, Dansky BS, Coffey SF, Saladin ME, Sonne S, Brady KT (2000) Cocaine dependence with and without post-traumatic stress disorder: a comparison of substance use, trauma history and psychiatric comorbidity. Am J Addict 9(1):51–62 CrossRefPubMed
Zurück zum Zitat Becker JB, Prendergast BJ, Liang JW (2016) Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ 7:34 CrossRefPubMedPubMedCentral Becker JB, Prendergast BJ, Liang JW (2016) Female rats are not more variable than male rats: a meta-analysis of neuroscience studies. Biol Sex Differ 7:34 CrossRefPubMedPubMedCentral
Zurück zum Zitat Chilcoat HD, Breslau N (1998) Investigations of causal pathways between PTSD and drug use disorders. Addict Behav 23(6):827–840 CrossRefPubMed Chilcoat HD, Breslau N (1998) Investigations of causal pathways between PTSD and drug use disorders. Addict Behav 23(6):827–840 CrossRefPubMed
Zurück zum Zitat Coffey SF, Saladin ME, Drobes DJ, Brady KT, Dansky BS, Kilpatrick DG (2002) Trauma and substance cue reactivity in individuals with comorbid posttraumatic stress disorder and cocaine or alcohol dependence. Drug Alcohol Depend 65(2):115–127 CrossRefPubMed Coffey SF, Saladin ME, Drobes DJ, Brady KT, Dansky BS, Kilpatrick DG (2002) Trauma and substance cue reactivity in individuals with comorbid posttraumatic stress disorder and cocaine or alcohol dependence. Drug Alcohol Depend 65(2):115–127 CrossRefPubMed
Zurück zum Zitat Erhardt E, Zibetti LCE, Godinho JM, Bacchieri B, Barros HMT (2006) Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin. Braz J Med Biol Res 39:1625–1635 CrossRefPubMed Erhardt E, Zibetti LCE, Godinho JM, Bacchieri B, Barros HMT (2006) Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin. Braz J Med Biol Res 39:1625–1635 CrossRefPubMed
Zurück zum Zitat Gao J, Wang H, Liu Y, Li YY, Chen C, Liu LM, Wu YM, Li S, Yang C (2014) Glutamate and GABA imbalance promotes neuronal apoptosis in hippocampus after stress. Med Sci Monit 20:499–512 CrossRefPubMedPubMedCentral Gao J, Wang H, Liu Y, Li YY, Chen C, Liu LM, Wu YM, Li S, Yang C (2014) Glutamate and GABA imbalance promotes neuronal apoptosis in hippocampus after stress. Med Sci Monit 20:499–512 CrossRefPubMedPubMedCentral
Zurück zum Zitat Hammad SM, Truman J-P, Al Gadban MM, Smith KJ, Twal WO, Hamner MB (2012) Altered blood sphingolipidomics and elevated plasma inflammatory cytokines in combat veterans with post-traumatic stress disorder. Neurobiol Lipids 10:2 PubMed Hammad SM, Truman J-P, Al Gadban MM, Smith KJ, Twal WO, Hamner MB (2012) Altered blood sphingolipidomics and elevated plasma inflammatory cytokines in combat veterans with post-traumatic stress disorder. Neurobiol Lipids 10:2 PubMed
Zurück zum Zitat Lguensat A, Boudjafad Z, Giorla E, Bennis M, Baunez C, Garcia R, Ba-M’hamed S (2021) Repeated ethanol exposure following avoidance conditioning impairs avoidance extinction and modifies conditioning-associated prefrontal dendritic changes in a mouse model of post-traumatic stress disorder. [Manuscript submitted for publication] Lguensat A, Boudjafad Z, Giorla E, Bennis M, Baunez C, Garcia R, Ba-M’hamed S (2021) Repeated ethanol exposure following avoidance conditioning impairs avoidance extinction and modifies conditioning-associated prefrontal dendritic changes in a mouse model of post-traumatic stress disorder. [Manuscript submitted for publication]
Zurück zum Zitat Müller CP, Carey RJ, Wilkisz M, Schwenzner S, Jocham G, Huston JP, De Souza Silva MA (2008) Acute anxiolytic effects of cocaine: the role of test latency and activity phase. Pharmacol Biochem Behav 89(2):218–226 CrossRefPubMed Müller CP, Carey RJ, Wilkisz M, Schwenzner S, Jocham G, Huston JP, De Souza Silva MA (2008) Acute anxiolytic effects of cocaine: the role of test latency and activity phase. Pharmacol Biochem Behav 89(2):218–226 CrossRefPubMed
Zurück zum Zitat Nutt DJ, Malizia AL (2004) Structural and functional brain changes in posttraumatic stress disorder. J Clin Psychiatry 65(Suppl 1):11–17 PubMed Nutt DJ, Malizia AL (2004) Structural and functional brain changes in posttraumatic stress disorder. J Clin Psychiatry 65(Suppl 1):11–17 PubMed
Zurück zum Zitat Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press
Zurück zum Zitat Peng Z, Wang H, Zhang R, Chen Y, Xue F, Nie H, Chen Y, Wu D, Wang Y, Wang H, Tan Q (2013) Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1β level and p38 MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress disorder. Physiol Res 62(5):537–545 CrossRefPubMed Peng Z, Wang H, Zhang R, Chen Y, Xue F, Nie H, Chen Y, Wu D, Wang Y, Wang H, Tan Q (2013) Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1β level and p38 MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress disorder. Physiol Res 62(5):537–545 CrossRefPubMed
Zurück zum Zitat Rodriguez A, Zhang H, Klaminder J, Brodin T, Andersson M (2017) ToxId: an algorithm to track the identity of multiple animals. Sci Rep 7(1):14774 CrossRefPubMedPubMedCentral Rodriguez A, Zhang H, Klaminder J, Brodin T, Andersson M (2017) ToxId: an algorithm to track the identity of multiple animals. Sci Rep 7(1):14774 CrossRefPubMedPubMedCentral
Zurück zum Zitat Rodriguez A, Zhang H, Klaminder J, Brodin T, Andersson PL, Andersson M (2018) ToxTrac: a fast and robust software for tracking organisms. Methods Ecol Evol 9(3):460–464 CrossRef Rodriguez A, Zhang H, Klaminder J, Brodin T, Andersson PL, Andersson M (2018) ToxTrac: a fast and robust software for tracking organisms. Methods Ecol Evol 9(3):460–464 CrossRef
Zurück zum Zitat Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G (1995) Brain corticotropin-releasing factor mediates anxiety-like behavior induced by cocaine withdrawal in rats. Brain Res 675:89–97 CrossRefPubMed Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G (1995) Brain corticotropin-releasing factor mediates anxiety-like behavior induced by cocaine withdrawal in rats. Brain Res 675:89–97 CrossRefPubMed
Zurück zum Zitat Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20 CrossRefPubMed Shaham Y, Shalev U, Lu L, De Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology 168:3–20 CrossRefPubMed
Zurück zum Zitat Sheynin J, Shind C, Radell M, Ebanks-Williams Y, Gilbertson MW, Beck KD, Myers CE (2017) Greater avoidance behavior in individuals with posttraumatic stress disorder symptoms. Stress 20(3):285–293 CrossRefPubMedPubMedCentral Sheynin J, Shind C, Radell M, Ebanks-Williams Y, Gilbertson MW, Beck KD, Myers CE (2017) Greater avoidance behavior in individuals with posttraumatic stress disorder symptoms. Stress 20(3):285–293 CrossRefPubMedPubMedCentral
Zurück zum Zitat Siegmund A, Wotjak CT (2007) A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitised fear. J Psychiatr Res 41(10):848–860 CrossRefPubMed Siegmund A, Wotjak CT (2007) A mouse model of posttraumatic stress disorder that distinguishes between conditioned and sensitised fear. J Psychiatr Res 41(10):848–860 CrossRefPubMed
Zurück zum Zitat Wang B, Luo F, Zhang WT, Han JS (2000) Stress or drug priming induces reinstatement of extinguished conditioned place preference. NeuroReport 11:2781–2784 CrossRefPubMed Wang B, Luo F, Zhang WT, Han JS (2000) Stress or drug priming induces reinstatement of extinguished conditioned place preference. NeuroReport 11:2781–2784 CrossRefPubMed
Zurück zum Zitat Zohar J, Juven-Wetzler A, Sonnino R, Cwikel-Hamzany S, Balaban E, Cohen H (2011) New insights into secondary prevention in post-traumatic stress disorder. Dialog Clin Neurosci 13(3):301–309 CrossRef Zohar J, Juven-Wetzler A, Sonnino R, Cwikel-Hamzany S, Balaban E, Cohen H (2011) New insights into secondary prevention in post-traumatic stress disorder. Dialog Clin Neurosci 13(3):301–309 CrossRef
Metadaten
Titel
Repeated cocaine exposure prior to fear conditioning induces persistency of PTSD-like symptoms and enhancement of hippocampal and amygdala cell density in male rats
verfasst von
Asmae Lguensat
Christian Montanari
Cassandre Vielle
Mohamed Bennis
Saadia Ba-M’hamed
Christelle Baunez
René Garcia
Publikationsdatum
30.06.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 7/2021
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02320-w