Exaggerated cue-induced reinstatement of cocaine seeking but not incubation of cocaine craving in a developmental rat model of schizophrenia

Abstract

Rationale Patients with schizophrenia exhibit high comorbidity for substance abuse, but the biological underpinnings of this dual diagnosis condition are still unclear. Previous studies have shown that rats with a neonatal ventral hippocampal lesion (NVHL), a widely used developmental animal model of schizophrenia, exhibit increased cocaine and methamphetamine self-administration, and cocaine-induced reinstatement. Objective Here, we assessed whether a NVHL would also potentiate cue-induced reinstatement of cocaine seeking and the time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving) in adult rats. Methods Rats were trained to self-administer cocaine (3 or 6 h/day, 0.75 mg/kg/infusion paired with a tone-light cue) for 10 days, followed by extinction training (3 h/day), and cue-induced reinstatement of cocaine seeking. Other rats were tested for incubation of cocaine craving, assessed in extinction tests 1 and 30 days after the last self-administration session. Results Although there was no significant difference in cocaine intake between NVHL and sham controls, NVHL rats took significantly longer to reach an a priori set extinction criterion and exhibited enhanced cue-induced reinstatement. However, while cue-induced cocaine seeking was higher after 30 days than after 1 day of withdrawal (incubation of cocaine craving), the NVHL had no effect on this incubation. Conclusion These data confirm previous reports on enhanced resistance to extinction after NVHL and demonstrate that NVHL rats exhibit enhanced cue-induced reinstatement of cocaine seeking after extinction, a measure of drug relapse.

Light alcohol intake during adolescence induces alcohol addiction in a neurodevelopmental model of schizophrenia

“…In a recent study, a similar increased self‐administration in NVHL rats as compared with controls has been shown for cocaine in a reinstatement paradigm (Karlsson et al . ). A main finding in this report is that NVHL rats demonstrated resistance to extinguish their alcohol operant responding.…”

Protracted maturation of forebrain afferent connections of the ventral tegmental area in the rat

“…PND, postnatal day. [1] Albert et al, ; [2] Baldini et al, ; [3] Crawford et al, ; [4] Fleming et al, ; [5] Du and Grace, ; [6] Karlsson et al, ; [7] Saul et al, ; [8] Schneider, ; [9] Suo et al, ; [10] Zitman and Richter‐Levin, ; [11] Schulz et al, ; [12] Schulz et al, ; [13] Sherrill et al, 2010; [14] Suri et al, ; [15] Zoratto et al, ; [16] Bhardwaj et al, ; [17] Clinton et al, ; [18] Dalton et al, ; [19] Damborsky et al, ; [20] Vazquez‐Roque et al, ; [21] Klug and van den Buuse, ; [22] McFadden et al, ; [23] Nielsen et al, ; [24] Pocivavsek et al, ; [25] Rosenfeld and Weller, ; [26] Shipman and Nicoll, ; [27] Van Hasselt et al, ; [28] Vetreno and Crews, ; [29] Avital et al, ; [30] Crawford et al, ; [31] Huppe‐Gourgues and O'Donnell, 2011a; [32] Huppe‐Gourgues and O'Donnell, 2011b; [33] Schwarz et al, ; [34] Trezza et al, ; [35] Turner et al, ; [36] Wright et al, ; [37] Carboni et al, ; [38] Pian et al, ; [39] Philpot et al, ; [40] Schramm‐Sapyta et al, ; [41] Andersen et al, ; [42] Benoit‐Marand and O'Donnell, ; [43] Tseng and O'Donnell ; [44] Badanich et al, ; [45] Andersen, ; [46] Tseng and O'Donnell, ; [47] Andersen ; [48] Badanich and Kirstein, ; [49] Pistis et al, ; [50] Spear, .…”

“…1). With this consensus in Baldini et al, 2013;[3] Crawford et al, 2013;[4] Fleming et al, 2013;[5] Du and Grace, 2013;[6] Karlsson et al, 2013;[7] Saul et al, 2013;[8] Schneider, 2013;[9] Suo et al, 2013;[10] Zitman and Richter-Levin, 2013;[11] Schulz et al, 2013a;[12] Schulz et al, 2013b;[13] Sherrill et al, 2010;[14] Suri et al, 2013;[15] Zoratto et al, 2013;[16] Bhardwaj et al, 2012;[17] Clinton et al, 2012;[18] Dalton et al, 2012;[19] Damborsky et al, 2012;[20] Vazquez-Roque et al, 2012;[21] Klug and van den Buuse, 2012;[22] McFadden et al, 2012;[23] Nielsen et al, 2012;[24] Pocivavsek et al, 2012;[25] Rosenfeld and Weller, 2012;[26] Shipman and Nicoll, 2012;[27] Van Hasselt et al, 2012;[28] Vetreno and Crews, 2012;[29] Avital et al, 2011;…”

Effects of addictive drugs on adult neural stem/progenitor cells

“…Stress, for example, was shown to play a complex role in triggering relapse among cocaine and heroin users [31]. It was also found in a developmental rat model that schizophrenia is associated with exaggerated cue-induced reinstatement of cocaine use [32]. The most direct evidence was shown by Noonan et al, who suppressed hippocampal neurogenesis in adult rats via cranial irradiation before drug use [33].…”