Ž . Brain Research 824 1999 304–307 Short communication Regulation of CCK mRNA expression in the rat brain by stress and treatment with sertraline, a selective serotonin re-uptake inhibitor Luciana Giardino a, ) , Carla Bettelli b , Monica Pozza b , Laura Calza b,c ` a Institute of Otolaryngology II, UniÕersity of Milano, Milan, Italy b Pathophysiology Center for the NerÕous System, Hesperia Hospital, Modena, Italy c Department of Biochemistry and Human Physiology, UniÕersity of Cagliari, Cagliari, Italy Accepted 9 February 1999 Abstract In this paper, we have investigated the regulation of CCK mRNA expression in the brain after restraint stress with and without long-term treatment with the selective serotonin reuptake inhibitor sertraline. Stress alone increases CCK mRNA levels in the hippocampus, whereas no changes were found in the cerebral cortex, amygdaloid complex and thalamus. CCK mRNA expression decreases in the hippocampus, increases in the thalamus and was not modified in the cerebral cortex and amygdaloid complex after sertraline alone. CCK mRNA content was unchanged in all investigated areas after stress plus sertraline compared to control rats. q 1999 Published by Elsevier Science B.V. All rights reserved. Keywords: CCK mRNA; Restraint stress; Sertraline; Rat; In situ hybridization Over the past decade, several studies in animals and humans have supported the hypothesis that the gut-brain Ž . peptide cholecystokinin CCK , is involved in the neurobi- w x ology of anxiety and panic attacks 10,19 . CCK fragments are panic attack inducing agents in healthy volunteers and w x in patients with panic disorders 18 , whereas CCK recep- tor antagonists attenuate the anxiogenic influence of CCK wx agonists 1 . A polymorphism in the CCK promoter has been found in persons with panic disorders, suggesting that this mutation can increase vulnerability to panic disorders w x 20 . Recent data from research trials suggest that serotonin Ž . selective reuptake inhibitors SSRIs are useful drugs in w x panic disorder 16 , being more effective and better toler- w x ated medications than those previously available 9,15 . In this paper, we investigated the CCK mRNA modifi- cation in stressful conditions in rats, after different types of sertraline treatments, and in combined situations of re- straint stress and sertraline treatments in target areas of ) Corresponding author. Pathophysiology Center for the Nervous Sys- tem, Hesperia Hospital, Via Arqua 80rA, 41100 Modena, Italy. Fax: ` q39-59-394840; E-mail: cefisnmo@hesperia.it serotoninergic ascending projection. The restraint model without rat immobilisation was used as middle stress and restraint was applied for 10 consecutive days, in order to avoid depression-like conditions due to more prolonged wx stress 5 . Thus, sertraline was co-administered with stress for 10 days. However, since many reports suggest a longer delay for the onset of sertraline action, we also treated a group of rats with sertraline for 18 days prior the stress sessions. Ž Male, Sprague–Dawley albino rats CD, Charles River, . Como, Italy , 150–175 g body weight, were used. The rats were allowed to adapt to the animal room for 1 week before beginning the experiments. During this period the animals were handled daily. Rats were divided into six Ž . groups: control saline-injected rats N s 8; sertraline- Ž . treated rats, 28 days N s 8 ; sertraline-treated rats, 10 Ž . Ž . days N s 8 ; stressed rats, 10 days N s 8 ; stressed rats Ž . treated with sertraline, 10 days N s 8 ; sertraline-treated rats, 28 days plus restraint stress last 10 days of sertraline Ž . treatment N s 8 . The animals were stressed daily for 2 h in the morning for 10 consecutive days. Rats were immo- Ž bilised in individual plastic tubes length 190 mm, internal . diameter 72 mm, with pores and sertraline hydrochloride 0006-8993r99r$ - see front matter q 1999 Published by Elsevier Science B.V. All rights reserved. Ž . PII: S0006-8993 99 01242-1