Motivational Responses to Natural and Drug Rewards in Rats with Neonatal Ventral Hippocampal Lesions An Animal Model of Dual Diagnosis Schizophrenia
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The high prevalence of substance use disorders in schizophrenia relative to the general population and other psychiatric diagnoses could result from developmental neuropathology in hippocampal and cortical structures that underlie schizophrenia. In this study, we tested the effects of neonatal ventral hippocampal lesions on instrumental behavior reinforced by sucrose pellets and intravenous cocaine injections. Lesioned rats acquired sucrose self-administration faster than sham-lesioned rats, but rates of extinction were not altered. Lesioned rats also responded at higher rates during acquisition of cocaine self-administration, and tended to acquire self-administration faster. Higher response rates reflected perseveration of responding during the post-injection "time-out" periods, and a greater incidence of binge-like cocaine intake, which persisted even after cocaine self-administration stabilized. In contrast to sucrose, extinction from cocaine self-administration was prolonged in lesioned rats, and reinstatement of cocaine seeking induced by cocaine priming increased compared with shams. These results suggest that neonatal ventral hippocampal lesions facilitate instrumental learning for both natural and drug rewards, and reduce inhibitory control over cocaine taking while promoting cocaine seeking and relapse after withdrawal. The findings are discussed in terms of possible developmental or direct effects of the lesions, and both positive reinforcement (substance use vulnerability as a primary disease symptom) and negative reinforcement (self-medication) theories of substance use comorbidity in schizophrenia.
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Adult rats with a NVHL show hyperlocomotion, increased response to novelty, abnormal social behaviors, exaggerated responses to stress, stimulants and NMDA antagonists, and increased liability for addictive behaviors.
“Behaviorally, adult rats with a NVHL show hyperlocomotion, 39,40 increased response to novelty, 41 abnormal social behaviors, 41 exaggerated responses to stress, stimulants and NMDA antagonists, 39,42 and increased liability for addictive behaviors.43,44”
From Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models (2011) · cites this paper as [43]
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- Authors
- Chambers, R.
- Affiliations
- Yale University (US)
- Corresponding author
- Chambers, R
- Venue
- Neuropsychopharmacology
- Published
- 2002-12
- Volume
- 27
- Issue
- 6
- Pages
- 889-905
- ISSN
- 0893-133X (ISSN-L)
- PMC
- PMC2919158
- OpenAlex
- W2113631648
- Cited by
- 111
- References
- 64
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 1 · 2014: 5 · 2013: 5 · 2012: 4
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- U.S. Public Health Service
- National Institute on Drug Abuse (R29DA010460, DA10460, R01DA010460)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- schizophrenia, dual diagnosis, substance use disorders, cocaine self-administration, sucrose self-administration, ventral hippocampus, operant conditioning, extinction, cocaine seeking, cocaine priming, self-medication, negative reinforcement, positive reinforcement, inhibitory control
- MeSH terms
- Animals, Animals, Newborn, Disease Models, Animal, Extinction, Psychological, Female, Hippocampus, Male, Motivation, Pregnancy, Reward, Schizophrenia, Self Administration, Behavior, Addictive, Rats, Sprague-Dawley, Diagnosis, Dual (Psychiatry), Cocaine-Related Disorders, Rats
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