Peptides, Vol. 10, pp. 95-101.© PergamonPress plc, 1989. Printedin the U.S.A. 0196-9781/89 $3.00 + .00 Effects of ICV Administration of Neurotensin and Analogs on EEG in Rats MARIE-NOELLE CASTEL, JEAN-MARIE STUTZMANN, MICHELLE LUCAS, JOSEPHINE LAFFORGUE AND JEAN-CHARLES BLANCHARD RhOne-Poulenc Santd, D~partement Biologie, Centre de Recherches de Vitry 13, Quai Jules Guesde, 94403 Vitry sur Seine Cedex, France Received 21 April 1988 CASTEL, M.-N., J.-M. STUTZMANN, M. LUCAS, J. LAFFORGUE AND J.-C. BLANCHARD. Effects of ICV administration of neurotensin and analogs on EEG in rats. PEPTIDES 10(1) 95-101, 1989.-The electroencephalographic (EEG) effects of the ICV administration of neurotensin (NT 1-13), NT 1-8 (an inactive neurotensin fragment) and D TYR- 11 NT (a long-lasting analog of neurotensin) were studied in rats. In awake rats, NT 1-13 (30 #g) and D TYR-11 NT (10 #g) induced an increase of the power spectrum in the theta range activity (4-7 Hz). In rats recorded during the sleep-wakefulness cycles, NT 1-13 (10 and 30/zg) and D TYR-11 NT (10 #g) had an awakening effect and also induced an increase of latency to the first episode of the different sleep stages (intermediate stage and slow wave sleep). NT 1-8 (30 and 90 #g in awake rats, 10 and 90 #g for sleep-wakefulness cycles)was inactivein all these experiments. Thus, it seems that all these effects can be linked to neurotensin receptors; indeed only fragments which recognize receptors possess an EEG activity. Neurotensin Neurotensin analogs ICV administration EEG Sleep-wakefulness cycles Spectral analysis Rats NEUROTENSIN (NT 1-13) is a tridecapeptide which was iso- lated from bovine hypothalami (4), sequenced (5) and synthe- tized (6) by Carraway and Leeman. Immunohistochemical studies revealed NT-like immunoreactivity in neuronal cell bod- ies, fibers and terminals localized in the substantia nigra, the bed nucleus of the stria terminalis, the central amygdaloid nucleus, the ventral tegmental area, the median eminence and the hypothalamus (17, 34, 35). Specific receptors for radiola- beled NT 1-13 were found in a heterogeneous distribution throughout the brain (33,38). More recently, nonspecific NT 1- 13 binding sites were identified in the murine central nervous system (CNS) (31). It is now well recognized that NT 1-13 could play a neurotransmitter role in the CNS (33). This peptide shares several pharmacological properties with neuroleptics. Particularly, NT 1-13 induces a diminution of locomotor activity (25, 26, 37), a muscle relaxation (25), a re- duction of food consumption (11) and a potentiation of seda- tion induced by barbiturates and ethanol (22). In addition, single and repeated administration of a neuroleptic (for exam- ple, haloperidol) can increase the NT 1-13 content in some cerebral structures (10). Many studies have demonstrated the colocalization of NT 1-13 and catecholamines (dopamine and norepinephrine) in cerebral structures implicated in the regulation of sleep-wake- fulness cycles (15, 21, 24). Since then, several reports have shown that catecholamines (20) and neuroleptics (8,13) can modify the electroencephalo- graphic (EEG) activity during stages of sleep and awakening. Thus, this study was designed to determine the consequences of intracerebroventricular (ICV) administration of NT 1-13 and analogs on the electrocorticogram (ECoG) of awake unre- strained rats and on the sleep-wakefulness cycles of freely mov- ing rats. The analogs chosen were NT 1-8, a neurotensin fragment which is inactive in biochemical (12,19), electrophys- iological (1) and behavioral tests (9,30), and D TYR-11 NT, a long-lasting analog of neurotensin which has the same proper- ties as NT 1-13 except the effect on motility (18), but with an increase in the duration and the potency of the neurotensin effects (7, 27, 29). METHOD Animals Adult male Sprague-Dawley rats (C.O.B.S., Ch. River, France) weighing between 270-300 g were equipped with chronic bipolar cortical electrodes and cannula in the lateral ventricle for ICV injection. Surgery Rats were implanted with jeweller's screw electrodes in the frontal, parietal and occipital cortical areas of the brain (under pentobarbital anesthesia; 50 mg/kg, 5 ml/kg, IP). The electro- myogram (EMG) was recorded by means of 2 silver threads implanted into the nuchal musculature. The electrodes were joined to a small female connector (CONNECTRAL, France). All the rats were stereotaxically implanted with a stainless-steel cannula (23 mm length, 0.6 mm diameter) in the left lateral 95