Natural reward-related learning in rats with neonatal ventral hippocampal lesions and prior cocaine exposure

Abstract

Rational-Psychostimulant injections in rats have been shown to alter future performance in natural reward conditioning. These effects may represent a persistent impact of drugs on neurocircuits that interface cognitive and motivational processes, which may be further altered in neuropsychiatric conditions that entail increased addiction vulnerability.Objective-This study investigated whether a rat model of schizophrenia with cocaine addiction vulnerability shows altered natural reward conditioning with or without prior cocaine exposure.Methods-Adult rats with SHAM or neonatal ventral hippocampal lesions were given cocaine (15 mg/kg per day for 5 days) or saline injections, followed 7 days later by natural reward-conditioned learning. Over ten daily sessions, water-restricted rats were assessed for durations of head entries into a magazine during random water presentations, a conditioning stimulus phase predictive of the water reward, and an "inappropriate" phase when conditioning stimuli were absent and reward presentation would be delayed.Results-Over repeated sessions, lesioned and SHAM rats showed similar reductions in total magazine entry durations, with similar increases in the allocations of entry times during the water presentation. However, lesioned rats, especially those exposed to cocaine, demonstrated reduced allocations of magazine entry times during the conditioning stimulus phase, and increased allocations during the inappropriate phase.Conclusions-Intact natural reward motivation accompanied by deficient learning of complex contingencies to guide efficient reward approach may represent a form of impulsivity as an addiction vulnerability trait marker in an animal model of schizophrenia.

Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats

“…High FLETR values in NVHL rats captures two clinical attributes of schizophrenia patients: over-consumption of carbohydrate enriched-foods and cognitive deficits (McCreadie 2003). High FLETR values are also consistent with how NVHLs show increased natural-reward related impulsivity and behavioral disinhibition (Chambers et al 2005; Chambers and Self 2002; Placek et al 2013; Tseng et al 2008) in parallel to PFC-based deficits in decision-making in schizophrenia patients (Heerey et al 2008). …”

Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions

“…NVHLs impact the maturation and function of prefrontal cortical-ventral striatal circuits to which the ventral hippocampus directly projects, in multiple ways that correspond to neural and behavioral findings in human schizophrenia and subjects with addictions ( Liu et al 1998 ; Chambers et al 2001 ; Heerey, Bell-Warren & Gold 2008 ; Tseng et al 2009 ). Behaviorally, NVHL rats show baseline cognitive impulsivity in their approach to natural rewards that is worsened by prior cocaine history ( Chambers et al 2005 ), mirroring impulsivity found in populations with nicotine dependence and other addictions ( Bickel, Odum & Madden 1999 ). The present study identified impulsive and perseverative styles of nicotine seeking in the NVHL model like those previously shown in cocaine self-administration ( Chambers & Self 2002 ).…”

“…Behaviorally, NVHL rats show baseline cognitive impulsivity in their approach to natural rewards that is worsened by prior cocaine history (Chambers et al, 2005), mirroring impulsivity found in populations with nicotine dependence and other addictions (Bickel et al, 1999). The present study identified impulsive and perseverative styles of nicotine seeking in the NVHL model like those previously shown in cocaine self-administration (Chambers and Self, 2002).…”

Adult hippocampal neurogenesis in the pathogenesis of addiction and dual diagnosis disorders

“…In turn, these circuits and their motivational functions are modulated by the status of the hippocampus (Chambers et al, 2005, 2001, 2010). At the focal point of this anatomy, the NAC is the epicenter of information processing and memory that generates an animal’s motivational–behavioral repertoire.…”