Differential clonidine effects on EEG following lesions of the dorsal and median raphe nuclei in rats

The effects of clonidine on EEG activity and gross behavior were studied in rats with electrolytic lesions of the median (MR) and dorsal (DR) raphe nuclei. Lesioned animals showed significant depletion in forebrain serotonin concentrations. Clonidine (0.1 mg/kg and 0.2 mg/kg IP) produced synchronization in cortical EEG pattern and markedly increased alpha and theta activities in unlesioned animals. Clonidine treatment resulted also in a sedative response. In MR lesioned rats clonidine effect upon EEG was significantly reduced and, additionally, sedative response was not seen. On the other hand clonidine effect on EEG was markedly increased in rats with lesioned DR. These results are discussed on the basis of possible interaction between serotonergic and noradrenergic neurons in the brain.     

Increase in insulin response to glucose in the rat chronically treated with clonidine

Summary Effect of chronic clonidine treatment on the response to glucose of rat pancreatic B-cells was investigated. Clonidine treatment was carried out for 10 days by dissolving the drug into drinking water at a concentration of 10 g/ml. Control rats were given drug-free tap water. Serum insulin responses to glucose (750 mg/kg, i. v.) of clonidinetreated rats were much smaller than those of control rats. However, after 1 day's withdrawal of clonidine, the rise in the serum insulin level induced by glucose was approximately 2-fold larger in clonidine-treated rats as compared to that in control rats. Since clonidine treatment decreased body weight of the rat by 10%–20% in 10 days, the same experiments were carried out with rats whose body weight loss was made comparable to that of clonidine-treated rats by restricting food for 10 days. Then, some animals of the group thus treated had food-restriction discontinued for 1 day. In both of the above two groups, no increment in glucoseinduced rise in serum insulin level was observed. Islets of Langerhans isolated from clonidine-treated rats showed pronounced insulin releasing capacity in response to glucose. Insulin content per islet of the clonidine-treated rat was slightly larger than that of control rat. These results indicate that the enhancement of serum insulin response to glucose following clonidine treatment is mainly attributable to the hyper-responsiveness developed in the pancreatic B-cells.     

The nucleus accumbens and antidepressants: modulation of ergometrine-induced hyperactivity by typical and atypical antidepressants and neuroleptics in rats

This study assesses the behavioural significance of the (-)sulpiride binding sites in the rat nucleus accumbens that bind antidepressants with high affinity and neuroleptics with low affinity. The effects were measured by intra-accumbens injections of typical and atypical antidepressants or neuroleptics, either given alone or in combination with ergometrine (1 g/0.5 l per side) on rat locomotor activity in a familiar environment. In addition, the after-effects of the combined ergometrine-drug treatment upon locomotor activity were analyzed. The antidepressants shared a common profile of effects. Thus, none of the antidepressants significantly altered locomotor activity in naive rats. Moreover, each antidepressant produced after-effects which were similar to those elicited in the acute ergometrine experiments. However, some antidepressants (amitriptyline and zimelidine) potentiated the ergometrine response, while other antidepressants (desipramine, mianserin and clorgyline) attenuated this response. (-)Sulpiride (0.5 g) decreased the ergometrine response when given together with ergometrine or 48 h earlier. Haloperidol had to be given in a dose that was 20 times higher than that of (-)sulpiride in order to be effective. Clozapine (1–10 g) failed to alter the ergometrine response when given together with ergometrine. Only (-)sulpiride produced a dose-dependent attenuation of locomotor activity in naive rats. The present data are discussed in terms of the hypothesis that drugs with antidepressive effects mediate their behavioural effects via mesolimbic (-)sulpiride binding sites.     

The interference of tricyclic antidepressants with the central hypotensive effect of clonidine

From clinical experience it is known that the hypotensive action of clonidine may be antagonized by simultaneously administrated desipramine. In the present experiments it has been demonstrated that pretreatment of anaesthetized cats with desipramine, imipramine, amitryptyline and protryptyline reduced the central hypotensive action of clonidine. Since both clonidine and the tricyclic antidepressive drugs were administered via the vertebral artery in low doses it may be concluded that the interaction occurs in the CNS, i.e. the rhombencephalon. The experiments suggest that interaction between tricyclic antidepressants and clonidine is not restricted to desmethylimipramine. Therefore combination of clonidine with these drugs should be avoided.     

Ophthalmological and pharmacological studies after administration of clonidine in rats

Clonidine (0.3 mg/kg or more p.o.) induced corneal lesions in rats. Amitriptyline did not give rise to such alterations. Biomicroscopically, these clonidine-induced lesions presented as gradually differentiated focal opacities in the superficial layers of the corneal centre. The corneal alterations were accompanied by a viscous, in the main clear conjunctival secretion and a slight degree of conjunctival injection. The histopathological picture, on the 7th day of the study, was characterised either by intracellular oedema of the basal epithelial cells in the focal opacities, or by regions in which alternately, next to fully intact epithelium, the epithelium had been scintered down to one half of the normal thickness accompanied by marked eosinophilia.Studies on the factors influencing the corneal lesions clearly showed that 0.3 mg/kg clonidine p.o. leads to a reduction of 20–30% in lacrimal secretion (p < 0.05); an exophthalmus of more than 60 min duration (p < 0.001); and a significant reduction in blinking (p < 0.005) and wiping (p < 0.01).Pre-treatment with the adrenergic -blocker phentolamine significantly reduced the appearance of corneal lesions (p < 0.01), as did repeated moistening of the cornea with methocel (p < 0.005).The results indicate that the clonidine induced corneal and conjunctival alterations in the rat are to be interpreted as keratoconjunctivitis sicca.Unpublished studies in the rabbit (1.0 mg/kg), dog (3.0 mg/kg) and monkey (3.0 mg/kg) indicate that the corneal lesions in the rat are species specific, as the other three species showed no such corneal alterations subsequent to the administration of clonidine.

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Zusammenfassung Clonidin (in Dosen ab 0,3 mg/kg p.o.) verursachte Cornealäsionen bei Ratten. Amitriptylin verursachte derartige Alterationen nicht. Biomikroskopisch stellten sich diese Clonidin-induzierten Läsionen als graduell differente Trübungsherde in den oberflächlichen Schichten des Hornhautzentrums dar. Begleitet waren die cornealen Alterationen von einem zähen, meist klaren Konjunktivalsekret und einer mäßigen Injektion der Bindehäute. Das histopathologische Bild am 7. Versuchstag war entweder durch ein intrazelluläres Ödem der Basalzellen des Epithels im Trübungsbereich gekennzeichnet oder es fielen Areale auf, in denen wechselweise neben völlig intaktem Epithel dieses stellenweise auf die Hälfte der normalen Dicke zusammengesintert und stärker eosinophil tingiert war.Untersuchungen einzelner die Cornealäsionen beeinflussender Faktoren machten deutlich, daß 0,3 mg/kg Clonidin p.o. zu einer 20–30%igen Verminderung der Tränensekretion führen (p < 0,05), einen länger als 60 min anhaltenden Exophthalmus verursachen (p < 0,001) und eine signifikante Verminderung der Lidschlagfrequenz (p< 0.005) und Putzbewegungen (p < 0.01) bewirken. Die Vorbehandlung mit dem adrenergen -Blocker Phentolamin verminderte das Auftreten der Cornealäsionen signifikant (p < 0,01) ebenso die wiederholte Befeuchtung der Cornea mit Methocel (p < 0,005).Die vorliegenden Ergebnisse weisen darauf hin, daß die Clonidin-induzierten Cornea-und Conjunctivaalterationen bei der Ratte im Sinne einer Keratokonjunktivitis sicca zu interpretieren sind.Noch nicht veröffentlichte Untersuchungen an Kaninchen (1,0 mg/kg), Hunden (3,0 mg/kg) und Affen (3,0 mg/kg) zeigen, daß die Cornealäsionen der Ratte ein speziesspezifisches Geschehen darstellen, da bei diesen drei Versuchstierspezies vergleichbare Corneaalterationen nach Clonidingabe nicht beobachtet wurden.

     

Morphine-like effects of clonidine on the EEG,slow wave sleep and behavior in the dog

EEG, behavioral and autonomic effects of morphine and clonidine were compared in the unrestrained beagle dog placed in a dimly-lit, sound-attenuated chamber equipped with video monitors. Intravenous (i.v.) morphine (0.5, 1 and 2 mg/kg) and clonidine (11, 33 and 100 μg/kg) caused parallel dose-related increases in NREM sleep with clonidine being 43 times more potent than morphine. Other similar effects were: an initial transient EEG-behavioral dissociation, increases in spectral power (8–16 Hz); decreases in temperature and heart and respiratory rates; emesis, miosis and salivation. Intraventricular (i.v.t.) morphine (33, 100 and 300 μg) and clonidine (10 and 30 μg) caused qualitatively similar EEG, sleep and behavioral effects. Naloxone (30 μg/kg i.v.) prevented EEG synchrony and behavioral effects of i.v. morphine (1 mg/kg) but not those of i.v. clonidine (100 μg/kg). Yohimbine pretreatment (0.1 mg/kg i.v.) was more effective in antagonizing clonidine than morphine. These results suggest that morphine and clonidine induce similar EEG, behavioral and autonomic effects through actions upon different receptors on the same or parallel neural pathways. The results further emphasize the importance of an α₂-adrenergic-opiod interaction to regulate sleep in the dog.     

Effects of clonidine and BS 100-141 on the EEG sleep pattern in rats.

The effects of the peripheral and central alpha-adrenoceptor stimulant and antihypertensive agents clonidine and BS 100-141 (N-amidino-2[2,6-dichlorophenyl]acetamide - HCl) on EEG sleep patterns in rats and on blood pressure in pithed rats have been investigated. Whereas both compounds abolished paradoxical sleep (PS), clonidine, in contrast to BS 100-141, markedly increased the sleeping time. Both drugs caused a dose-dependent increase in the blood pressure of pithed rats. The pressor action was abolished by the alpha-adrenoceptor blocking agent phentolamine, but was not influenced by reserpine, indicating a direct stimulation of vascular alpha-adrenoceptors by both drugs. It is suggested that sedation or sleep induction by adrenergic drugs cannot be explained exclusively by an action on central alpha-adrenoceptors. Rather, the findings suggest that such an action may be involved in the modulation of PS.     

Norepinephrine, clonidine, and tricyclic antidepressants selectively stimulate carbohydrate ingestion through noradrenergic system of the paraventricular nucleus

Using a self-selection feeding procedure, the present experiments examined the impact of central and peripheral injection of the alpha-adrenergic agonist clonidine (CLON) and the tricyclic antidepressant drugs amitriptyline (AMIT) and chlorimipramine (CIMIP) on nutrient selection in the adult male rat. In tests with mixed diets or with separate sources of the 3 macronutrients (carbohydrate, protein, and fat) simultaneously available, the following results were obtained: Peripheral and paraventricular nucleus (PVN) injection of CLON stimulated total food intake and preferentially increased ingestion of carbohydrate. Little or no change in protein or fat intake was observed. This pattern of response is similar to that observed with norepinephrine. PVN injection of AMIT and peripheral injection of CIMIP also selectively enhanced carbohydrate intake. These drug effects on carbohydrate selection occurred under a variety of conditions, including with mixed diets and pure dietary nutrients; under ad lib and restricted feeding conditions; in short (1 hr) as well as long (6 hr) test intervals; and in the absence or presence of a change in total calorie intake. Based on this and other evidence, it is proposed that noradrenergic neurons innervating the PVN in the rat play a role in regulating carbohydrate selection, and that this neurochemical system mediates the stimulating action of CLON and antidepressants on carbohydrate ingestion.     

Comparative study of the effects of tianeptine and other antidepressants on the activity of medial septal neurons in rats anesthetized with urethane

Summary Tianeptine is a tricyclic antidepressant which enhances serotonin uptake in certain brain areas. Tianeptine has been reported to improve both working and reference memories in rodents. The effects of tianeptine on the spontaneous activity of medial septal neurons were studied in rats anesthetized with urethane. Systemic administrations (0.2–1 mg/kg i. v.) of tianeptine decreased the spontaneous activity and disorganized or suppressed the rhythmically bursting activity of medial septal neurons, in a dose related manner. Iontophoretic administrations of tianeptine did not modify the spontaneous activity of medial septal neurons. Changes of the bursting activity were inconsistent. However, tianeptine blocked partially or completely the inhibition induced by the serotonin in 68% of the cases. In contrast, other antidepressants (amitriptyline, clomipramine and fluoxetine) potentiated the inhibitory effect of serotonin in 50%–60% of the cases. Our results show that tianeptine, applied by iontophoresis, has an effect on the medial septal neurons which was opposite to that of other antidepressants. On the basis of our findings, it can be tentatively proposed that tianeptine may have a beneficial effect on memory by counteracting the serotonin-induced inhibition of medial septal neurons. Send offprint requests to M. H. Bassant at the above address     

EEG effects of IV infusion of pentylenetetrazol in rats: A model for screening and classifying antiepileptic compounds

In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristics of the PTZ-induced EEG paroxysms. Most compounds had moderate to potent anti-PTZ effects, as shown by the changes in the EEG temporal parameters. However, these effects depended on the drugs and doses. Cluster analysis showed that drugs and doses which evoked similar changes were closely related and were included in separate clusters with respect to one another. In particular, the present results showed that benzodiazepines and antiepileptics cluster differently in their effects. Thus, this model could be a useful tool for assessing new antiepileptic drugs.     

Influence of therapeutic and toxic doses of neuroleptics and antidepressants on energy metabolism of the isolated perfused rat brain

Summary The isolated perfused rat brain was used for a comparative study of the effects of promazine, imipramine, monodesmethyl promazine and desipramine on cerebral energy metabolism. After perfusion for 30 min or 1 h the brain levels of the following substrates and metabolites were estimated: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, pyruvate, lactate, -ketoglutarate, and ammonia. Drug concentrations of 5·10^–6 M and 10^–5 M in the perfusion medium caused a significant decrease of glucose-6-P alone. When the drug concentration was raised to a toxic range (10^–4 M), reflected in the EEG by the pattern of secondary discharges, an accumulation of P-creatine and glucose and a decrease of glycogen, glucose-6-P and ammonia occurred; the lactate/pyruvate ratios remained unchanged. As there were no qualitative differences between the effects of the investigated neuroleptics and antidepressants on cerebral metabolism, these effects might be unspecific and not correlated with the pharmacological action of the drugs.Presented in part at the spring meeting of the Deutsche Pharmakologische Gesellschaft, Mainz 1973 (Stock et al.).     

The effects of clonidine on the partial reinforcement extinction effect (PREE)

Clonidine has been reported to exert anti-anxiety effects in animals and man similar to those of benzodiazepines. The present experiment examined the effects of clonidine administration on the partial reinforcement extinction effect (PREE) which is known to be sensitive to benzodiazepine action. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Clonidine 50 g/kg was administered in a 2×2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. The PREE, i.e., increased resistance to extinction exhibited by PRF animals as compared to CRF animals, was obtained in animals that received saline in acquisition, independently of drug treatment in extinction, as well as in animals that received clonidine in both acquisition and extinction, but not in animals that received clonidine in acquisition alone. The administration of clonidine in extinction alone increased resistance to extinction in both the CRF and PRF animals. The increase in resistance to extinction, typically obtained with benzodiazepine treatment, indicates that clonidine exerts anxiolytic effects, supporting the involvement of the noradrenergic system in anxiety. However, clonidine did not fully reproduce the effects of benzodiazepines on the PREE, suggesting that the two classes of drugs may act via different noradrenergic mechanisms.     

Effects of single and repeated daily injections of morphine,clonidine, and l-nantradol on avoidance responding of rats

Interruption of a photobeam by rats was maintained under a continuous shock avoidance schedule, and moderate response rates were maintained at low shock frequencies. Responding decreased, and shock frequency increased, in a dose-dependent manner after acute injections of the narcotic morphine, the antihypertensive l-nantradol clonidine, and the cannabinoid l-nantradol. Clonidine and l-nantradol were about 100 times more potent than morphine for decreasing overall responding, and l-nantradol was about 3 times more potent than clonidine for decreasing escape responding. When drugs were given repeatedly prior to daily experimental sessions, tolerance developed to response rate decreases of morphine and l-nantradol within seven to ten sessions, but tolerance did not develop to rate decreases of clonidine for up to 30 sessions. Continued decreased responding by clonidine was antagonized by yohimbine, but not by prazosin or naltrexone. These results extend observations for the acute effects of l-nantradol and clonidine to operant responding under a schedule of continuous shock avoidance. Different potencies for drugs in the present and previous experiments suggest important effects of response topography on dose effects.     

Piperoxane reduces the effects of clonidine on aggression in mice and on noradrenaline dependent hypermotility in rats

Aggression in isolated male mice and hypermotility in rats produced by the noradrenaline releaser H 77/77 were studied after the s.c. administration of the alpha-adrenergic agonist clonidine and the alpha-antagonist piperoxane. Clonidine 0.005--0.5 mg/kg inhibited both behaviours while piperoxane showed a weak and short-lasting antiaggressive effect and no H 77/77 antagonism. Inactive doses of piperoxane reduced the inhibitory effects of clonidine. The results indicate that isolation-induced aggression in mice and H 77/77-induced hypermotility in rats are behavioural signs related to the availability of noradrenaline at the receptor.     

Effects of clonidine and guanfacine on drinking and ambulation in spontaneously hypertensive rats

Present experiment was undertaken to compare the effects of clonidine and guanfacine on water drinking behavior and ambulatory activity in spontaneously hypertensive rats (SHR). Equipotent hypotensive doses of clonidine and guanfacine, 150 micrograms/kg and 1500 micrograms/kg, respectively, given twice a day at 8:00 and 20:00, produced a triphasic pattern of behavioral changes; initial increase in water drinking and ambulation during the light period, decrease in water intake and ambulation at the beginning of the dark period, and a second increase in water drinking and ambulation at the end of the dark period. Guanfacine treated SHR showed less change in water drinking behavior and ambulation than the clonidine treated SHR.     

Effects of neuroleptic drugs,clonidine and lithium on the expression of conditioned behavioral excitation in rats

Rats with a history of daily (21 days) amphetamine (2.5 mg/kg) treatment showed enhanced activity when under placebo in their amphetamine-associated environment. We found that this conditioned effect was reduced by haloperidol (0.06; 0.125; 0.25 mg/kg), pimozide (0.25; 0.5 mg/kg) and sulpiride (8; 16; 32 mg/kg) but only at doses similar to or, in the case of pimozide, higher than those required to antagonize the unconditioned stimulant effects of amphetamine (2.5 mg/kg). Conversely, we observed that clonidine (7; 15; 30; 60 g/kg) or lithium regimen (between days 15 and 21) leading to lithium plasma levels of 1.3±0.1 mEq/1, abolished amphetamine-conditioned hyperactivity but did not affect the unconditioned stimulation of amphetamine or locomotor activity in control rats. Moreover, we found that hyperactivity induced by the daily anticipation of food delivery shared identical pharmacological sensitivity with the behavioural excitation produced by a conditioning history with amphetamine. In light of the antimanic properties of lithium and clonidine and the ability of this latter drug to reduce noradrenergic transmission, our findings raise the posibility that incentive activity may model noradrenergic-dependent aspects of mania.     

Influence of 6-hydroxydopamine on the behavioral effects induced by apomorphine or clonidine in rats

The aim of this paper is to examine if central chemical sympathectomy induced by two injections of 6-hydroxydopamine (6-OHDA) in a dose of 250 g intracerebroventricularly (k.c.v.) affects behavioral phenomena elicited by apomorphine (AP) (1 or 1.2 mg/kg i.p.) or clonidine (CL) (0.1 mg/kg, 5 or 1 g/kg i.p.).Experiments were carried out on male Wistar rats. The time of duration of several components of behavior and the degree of irritability of rats were measured. Moreover, open field and hole test were performed. The lower dose of AP did not affected behavior of rats. The higher dose increased the locomotor and exploratory activity of animals. 6-OHDA potentiated these effects of AP. CL (0.1 mg/kg) had a depressive effect on the rats' behavior, which was potentiated by 6-OHDA. CL (5 g/kg) had no effect on the rats' behavior, but in a dose of 1 g/kg caused excitatory behavior. This type of behavior was abolished by 6-OHDA. In conclusion, central chemical sympathectomy caused increased sensitivity of the central nervous system on AP. Excitatory behavioral effects of CL in low dosage may be connected with stimulation of central adrenergic receptors. Depressive behavioral effect of CL in high dosage is unspecific. Central chemical sympathectomy affects by different methods the reactivity of dopaminergic and noradrenergic neurons.     

Behaviour-related effects of nicotine on slow EEG waves in basal nucleus-lesioned rats

The basal magnocellular nucleus is assumed to play a crucial role in cholinergic activation of the cortical EEG. The aim of this study was to establish whether intraperitoneally applied nicotine may counteract the power asymmetry of the slow waves in the cortical EEG of both hemispheres after an unilateral lesion in the basal nucleus. In 17 rats the basal nucleus (substantia innominata/ventral pallidum) was unilaterally lesioned by ibotenic acid. The lesion produced unilateral power increases of all frequencies up to 20 Hz in the frontal EEG that increased with higher arousal level. Additionally, synchronized spike and wave discharges appeared in the frontal EEG. The results indicate that the basal nucleus suppresses especially the delta EEG waves in the frontal motor cortex during motor active behaviour. Nicotine (0.1 and 1 mg/kg) partially counteracts the power asymmetry of frontal slow waves (2–6 Hz) only during exploratory sniffing but not during grooming and waking immobility. Physostigmine (1 mg/kg) was also effective during exploratory sniffing. The results may indicate a role of nicotinic mechanisms in the information input component of exploratory behaviour.     

Co-treatment with antidepressants and aripiprazole reversed the MK-801-induced some negative symptoms of schizophrenia in rats

BackgroundSchizophrenia is a chronic, most devastating psychiatric illness that impairs mental and social functioning. A few clinical reports have suggested that antidepressant drugs are able to augment the activity of atypical antipsychotic drugs, thus effectively improving treatment of some negative symptoms of schizophrenia.MethodsThe aim of the present study was to investigate the effect of the antidepressant escitalopram or mirtazapine and aripiprazole (an atypical antipsychotic), given separately or jointly, on the deficits induced by MK-801(a noncompetitive N-methyl-d-aspartate receptor antagonist) in the social interaction test in male Sprague-Dawley rats. The social interaction was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. Antidepressants and aripiprazole were given 60 and 30 min before the test, respectively. WAY 100635 (a 5-HT_1A antagonist) and SCH 23390 (a dopamine D₁ antagonist) were give 20 min before the tests.ResultsThe present results showed that MK-801 (0.1 mg/kg)-induced deficits in the social interaction test. Aripiprazole (0.1 and 0.3 mg/kg) reversed those effects. Co-treatment with an ineffective dose of aripiprazole (0.03 mg/kg) and escitalopram (5 and 10 mg/kg) or mirtazapine (5 mg/kg) abolished the deficits evoked by MK-801, and those effects were especially blocked by a 5-HT_1A receptor antagonist (WAY 100635) or partly by dopamine D₁ receptor antagonist (SCH 23390).ConclusionsThe obtained results suggest that amelioration of the antipsychotic-like effect of aripiprazole by antidepressants in the MK-801-induced some negative symptoms of schizophrenia in rats may be associated with serotonin 5-HT_1A and to a lesser degree with dopamine D₁ receptors.     

EEG effects of subcutaneous and intracerebroventricular injections of arginine vasopressin in the rat

Several studies have suggested that arginine vasopressin (AVP) may act centrally as a neurohormone or neuromodulator to produce electrophysiological and behavioral effects. However, there are few reports of EEG effects of AVP in unanesthetized, behaving animals. In the present study the EEG effects of behaviorally relevant subcutaneous (SC) doses of AVP (6 g/kg) known to raise blood pressure were compared to behaviorally relevant intracerebroventricular (ICV) doses (0.1–1.0 ng) and multiple toxic ICV doses (1.0 g) of AVP. Central injections of toxic doses of AVP produced behavioral arrest, bodily barrel rolling, and EEG slowing, but did not induce electrographic signs of seizure activity. Comparison of the spectral characteristics of the EEG revealed some similarities in the distribution of power between SC and the 1.0 ng ICV dose; whereas ICV doses of 0.1 and 0.5 ng produced power distributions that were different from those seen following saline or SC doses of AVP. The similarities in EEG activity between SC injections and the 1.0 ng ICV dose suggest a common brain state may be induced by the two routes of administration in those dose ranges.