R Andrew Chambers1, Jane R Taylor. 1. Laboratory for Translational Neuroscience of Dual Diagnosis Disorders (RAC), Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USA. robchamb@iupui.edu
Abstract
BACKGROUND: Increased substance disorder comorbidity in schizophrenia may reflect greater vulnerability to addictive processes because of inherent neurocircuit dysfunction in the schizophrenic brain. METHODS: To further explore this hypothesis, we used neonatal ventral hippocampal lesions (NVHL) as a rat model of schizophrenia and assessed locomotor sensitization to cocaine (15 mg/kg) in adulthood. RESULTS: The NVHL animals showed greater activity in response to an initial cocaine injection compared with sham and saline-treated groups. With daily cocaine injections over 7 days, NVHL rats showed elevated locomotor sensitization curves with greater fluctuations in the intersession changes in activity between days 4 and 7. In a single session 4 weeks later, NVHL compared with SHAM rats showed maintenance of cocaine-associated hyperactivity, as if superimposed on long-term sensitization effects present in both groups. CONCLUSIONS: In a neurodevelopmental model of schizophrenia, the locomotor effects of cocaine were augmented on initial and repeated doses, with emergence of irregularity in sensitization-related changes in activity in the short term and perseverance of augmented effects in the long term. Altered patterns of behavioral sensitization, as a possible correlate of greater addiction vulnerability, can occur as a by-product of neural systems dysfunction responsible for major psychiatric syndromes.
BACKGROUND: Increased substance disorder comorbidity in schizophrenia may reflect greater vulnerability to addictive processes because of inherent neurocircuit dysfunction in the schizophrenic brain. METHODS: To further explore this hypothesis, we used neonatal ventral hippocampal lesions (NVHL) as a rat model of schizophrenia and assessed locomotor sensitization to cocaine (15 mg/kg) in adulthood. RESULTS: The NVHL animals showed greater activity in response to an initial cocaine injection compared with sham and saline-treated groups. With daily cocaine injections over 7 days, NVHL rats showed elevated locomotor sensitization curves with greater fluctuations in the intersession changes in activity between days 4 and 7. In a single session 4 weeks later, NVHL compared with SHAM rats showed maintenance of cocaine-associated hyperactivity, as if superimposed on long-term sensitization effects present in both groups. CONCLUSIONS: In a neurodevelopmental model of schizophrenia, the locomotor effects of cocaine were augmented on initial and repeated doses, with emergence of irregularity in sensitization-related changes in activity in the short term and perseverance of augmented effects in the long term. Altered patterns of behavioral sensitization, as a possible correlate of greater addiction vulnerability, can occur as a by-product of neural systems dysfunction responsible for major psychiatric syndromes.
Authors: Jill M Williams; Kunal K Gandhi; Shou-En Lu; Marc L Steinberg; Neal L Benowitz Journal: Nicotine Tob Res Date: 2012-02-07 Impact factor: 4.244
Authors: R Andrew Chambers; Alena M Sentir; Susan K Conroy; William A Truitt; Anantha Shekhar Journal: Biol Psychiatry Date: 2009-10-31 Impact factor: 13.382
Authors: R A Chambers; J N McClintick; A M Sentir; S A Berg; M Runyan; K H Choi; H J Edenberg Journal: Genes Brain Behav Date: 2013-06-22 Impact factor: 3.449