Motivational Responses to Natural and Drug Rewards in Rats with Neonatal Ventral Hippocampal Lesions An Animal Model of Dual Diagnosis Schizophrenia

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

“…As an animal model of increased SUD vulnerability in schizophrenia, NVHL rats selfadministering COC show increased drug-paired lever presses in acquisition, incidence of binging-like patterns of drug intake, increased drug seeking after drug withdrawal, and COCinduced reinstatement of drug seeking after extinction of drug seeking (Chambers and Self 2002). The lesion-induced alterations in cognitive/motivational performance identified in the present study may represent an endophenotypic-like trait marker of this addiction vulnerability.…”

“…Similarly, to the extent that total durations of magazine entries over conditioning may reflect motivated effort or non-specific seeking behavior for the water reward, the absence of lesion effects on this measure, or on the proportional durations of magazine entries during the water presentation (UCS phase), do not support an interpretation whereby lesion effects on the CS or INA measures resulted from significant differences in reward motivation per se. However, since NVHL rats show profound deficits in working memory performance measured by food reward seeking on a radial arm maze (Chambers et al 1996), but increased lever pressing for food reward on a fixed-ratio 3 schedule (Chambers and Self 2002), the present results may reflect abnormal functioning of neural systems that integrate cognitive with motivational processes. NVHLs may compromise efficient reward acquisition requiring more complex learned associations (e.g., CS-UCS associations), while increasing motivational responding under more simple contingencies (e.g., achieving increasing proportions of UCS-targeted approaches via greater proportions of indiscriminate INA phase approaches).…”

“…Analogous findings have been observed in terms of the locomotor activating effects of COC injections in a separate study (Chambers and Taylor 2004): NVHL rats not only show hyperlocomotive responses to single psychostimulant injections, but also show elevated sensitization curves with daily COC injections when compared with SHAMs. Thus, in both natural reward-conditioned learning and locomotor sensitization studies, repeated COC injections in NVHL rats may more potently exacerbate phenotypic expression of behavioral markers of addictive drug exposure, consistent with the more robust installment of an addicted phenotype in COC self-administration (Chambers and Self 2002).…”

“…Among the initial findings characterizing the NVHL syndrome was hyperlocomotor responses to mild stressors and contextual novelty (Lipska et al 1993), while subsequent studies identified decreased preference for a sweetened water supply during water restriction (Le Pen et al 2002), but increased rates of instrumental responding for sucrose reward during food restriction (Chambers and Self 2002). Because lesion status did not produce significant effects on durations of UCS phase or non-UCS phase magazine entries in the initial magazine training session, or on total durations of magazine entries across the 10 days of conditioned learning, group differences in non-specific locomotor activity, if present, did not translate into differences in exploration of the magazine.…”

“…NVHL rats show post-adolescent onset of neurolepticresponsive, positive-like symptoms, such as hyper-responsivity of dopamine-mediated behaviors (Lipska et al 1993;Lipska and Weinberger 1994) accompanied by a number of schizophrenia-related cognitive and negative-like symptoms Chambers et al 1996;Grecksch et al 1999;Lipska et al 1995). In applying this animal model toward understanding increased substance use disorder (SUD) comorbidity in schizophrenia, NVHL rats show increased vulnerability to developing an addicted phenotype in acquisition, maintenance and post-withdrawal phases of COC self-administration (Chambers and Self 2002). In the present study we tested rats with NVHL or SHAM lesions and recent history of sub-chronic COC exposure (15 mg/kg per day for 5 days) or saline (SAL) injections, on subsequent natural reward-conditioned learning.…”