Dr Mohammed Shoaib,
Institute of Neuroscience,
Newcastle upon Tyne, UK
Date: Thursday, 29 October 2015
Chairperson: A/Prof Gavin Dawe
Factors affecting tobacco smoking by patients with schizophrenia: focus on cognitive enhancement and reinforcing properties of nicotine in laboratory rodents
Cognitive deficits represent one of the core disabling symptoms within this disorder, accountable for the majority of disruption to everyday life. Over 80% of patients with schizophrenia smoke compared to just 30% of the general population, which has been postulated as a form of self-medication to remediate the cognitive symptoms. Our laboratory has shown that a sub-chronic, sub-anesthetic dosing regimen of the NMDA antagonist ketamine can induce cognitive deficits on a variety of cognitive domains such as memory capacity of working memory and executive decision-making in the attentional set-shifting task. The objective was to examine the effects of treating rats with ketamine (daily injection of 30mg/kg IP for 5 days) on acquisition to self-administer intravenous nicotine (0.015 & 0.03mg/kg/inj) using two-lever operant conditioning chambers. Following 5 days of a ‘washout’ period from the sub-chronic treatment, groups of rats (n=12) were given access to intravenous nicotine in 1 hr sessions under a fixed-ratio schedule of reinforcement. Both ketamine- and vehicle-treated subjects showed steady rates of acquisition with no significant difference between the treated groups. Differences were however apparent when rats were presented a choice between nicotine and sucrose (0.2ml of 5mg/ml solution) under a concurrent choice procedure (VR4). Over 3 three concurrent sessions, vehicle-treated rats migrated their responses exclusively to the sucrose lever, whilst ketamine-treated rats were resistant and made fewer responses on the sucrose lever but more importantly maintained their intake of nicotine. The results from this experiment suggest that the sub-chronic ketamine regimen used to model cognitive deficits associated with schizophrenia does not modify the primary reinforcing effects of nicotine. However, within value-based decision making in nicotine addiction, ketamine exposure made rats resistant to non-drug alternative reinforcers such as sucrose. These findings suggest that the high prevalence of tobacco smoking amongst people diagnosed with schizophrenia may represent self-medication in order to restore cognitive deficits, rather than an increase in their subjective feeling of satisfaction from the nicotine.