The importance of nitric oxide in social dysfunction.
Schizophrenia is a chronic disorder generally considered to encompass positive symptoms, negative symptoms and cognitive deficits. Increasing attention has been paid to the social cognitive deficits of the disorder as these dysfunctions are particularly handicapping, predictive of functional outcome and show poor treatment response. Phencyclidine (PCP) is a psychotomimetic drug used to model the different aspects of schizophrenia in experimental animal models. PCP-induced cognitive deficits and hyperlocomotion may be blocked by pretreatment with nitric oxide (NO) synthase inhibitors in rodents. The present study was carried out to evaluate the acute effects of PCP and NO synthase inhibition on social interaction in male Sprague-Dawley rats. The NO synthase inhibitor, L-NAME (10mg/kg) and PCP (2mg/kg) was injected subcutaneously to rats, which were then tested in pairs for social interactive behaviour. Twenty-four hours after the initial test a drug-free social interaction test was carried out to assess the rats' memory of the previous social interaction. The results showed that PCP reduced the time of social interaction on Day 1 compared to controls, and that pretreatment with the NO synthase inhibitor, L-NAME, attenuated this reduction towards control levels. Neither locomotor activity, nor frequency of social interactions were affected by the PCP treatment, suggesting that the PCP-induced effects observed were not due to drug-induced stereotypies. In combination with increasing clinical evidence for the involvement of NO in the pathophysiology of schizophrenia, the present results indicate that NO synthase inhibition may be a potentially new treatment strategy for alleviating social dysfunction in schizophrenia.
Wass
Caroline
C
Department of Pharmacology, The Institute of Neuroscience and Physiology, Sahlgrenska Academy University of Gothenburg, Sweden.
Klamer
Daniel
D
Fejgin
Kim
K
Pålsson
Erik
E
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology; D007279:Injections, Subcutaneous / Q000379:methods; D007398:Interpersonal Relations; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D006213:Hallucinogens; D009569:Nitric Oxide; D010622:Phencyclidine; D019331:NG-Nitroarginine Methyl Ester