ceruletide and Seizures

It is shown that both intracerebral and intraperitoneal neurotropin administration resulted in a decrease of seizure susceptibility of preliminary picrotoxin--kindled rats. On the other hand, neurotropin did not change the course of kindling development. Under conditions of acute picrotoxin--induced seizures it was observed that preliminary cycloheximide (protein-synthesis blocker) administration abolished anticonvulsant properties of neurotropin. It is concluded that anticonvulsant effects of neurotropin are realized via modulation of endogenous peptides synthesis and, in particular, cerulein.

Topics: Animals; Anticonvulsants; Ceruletide; Cycloheximide; Electroencephalography; Injections, Intraperitoneal; Injections, Intraventricular; Kindling, Neurologic; Male; Picrotoxin; Polysaccharides; Rats; Rats, Wistar; Seizures

Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.

Topics: Aggression; Animals; Behavior, Animal; Ceruletide; Dextroamphetamine; Diazepam; Electroshock; Haloperidol; Male; Mice; Motor Activity; Picrotoxin; Receptors, Cholecystokinin; Seizures

To study the possible involvements of neuropeptides in the occurrence of convulsion, pentylenetetrazol (PTZ) was given to male Wistar rats weighing 250-350 g, and the concentration of neurotensin (NT), and the maximal number of binding sites (Bmax) and dissociation constant (Kd) of NT receptor in the frontal cortex were measured. The effect of the pretreatment of thyrotropin-releasing hormone (TRH) or ceruletide (CER) on the convulsion was also studied. NT was extracted from the homogenates of rat frontal cortex by boiling, and measured by radioimmunoassay. Membrane fractions were incubated with increasing concentrations of 125I-NT. Nonspecific binding was determined in the presence of unlabeled NT and subtracted from total binding to obtain the specific binding. The Bmax and Kd were calculated by Scatchard analysis. Generalized convulsion appeared after intraperitoneal administration of 50 mg/kg PTZ with a latency of 68.2 +/- 4.4 sec. One hour after the administration, neurotensin-like immunoreactivity (NTLI) concentration was reduced from 4.7 +/- 0.6 to 2.3 +/- 0.1 ng/g wet wt (p less than 0.01) and the Bmax of NT receptor from 17.2 +/- 2.8 to 10.8 +/- 1.1 fmol/mg protein (p less than 0.01). However no significant changes were observed in somatostatin-like immunoreactivity (SSLI) concentration and the Bmax and Kd of SS receptor. These facts indicate that PTZ stimulates the release of NT resulting in down regulation of NT receptor. Pretreatment with intracerebroventricular (icv) administration of 30 micrograms/10 microliters NT 30 min before the 50 mg/kg PTZ administration shortened the duration of the convulsion from 135.0 +/- 42.8 to 11.5 +/- 11.9 sec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain; Ceruletide; Injections, Intraventricular; Male; Neuropeptides; Neurotensin; Pentylenetetrazole; Rats; Rats, Inbred Strains; Receptors, Neurotensin; Receptors, Neurotransmitter; Receptors, Somatostatin; Seizures; Somatostatin; Thyrotropin-Releasing Hormone

It has been shown in the behavioural experiments that combined pretreatment with haloperidol (0.25 mg/kg) and caerulein (40 micrograms/kg), and to a lesser extent pretreatment with caerulein alone caused long-term reversal of amphetamine (2 mg/kg) induced hyperexcitability in rats. Administration of proglumide (50 mg/kg), an antagonist of CCK-8 receptors, did not reverse long-term antiamphetamine effect of caerulein. In mice pretreatment with caerulein (50 and 100 micrograms/kg) alone or in combination with haloperidol (0.25 mg/kg) caused hypersensitivity to the behavioural effect of amphetamine (3 mg/kg). Intraventricular (I ng), but not systemic (100-500 micrograms/kg) administration of caerulein selectively antagonized seizures in mice induced by intraventricular administration of quinolinic acid (5 micrograms) and N-methyl-D-aspartate (0.2 microgram). Pretreatment with proglumide (50 mg/kg) reversed the anticonvulsive effect of caerulein in mice. In rats, caerulein failed to affect the seizures caused by intraventricular administration of quinolinic acid. The results of the present study demonstrate the existence of obvious interspecies differences in the behavioural effects of caerulein, the agonist of CCK-8 receptors, in mice and rats.

Topics: Amphetamine; Animals; Behavior, Animal; Ceruletide; Drug Interactions; Haloperidol; Male; Mice; Motor Activity; Rats; Receptors, Cholecystokinin; Seizures; Species Specificity; Time Factors

Subcutaneous administration of caerulein (100-500 micrograms/kg) significantly reduced the development of picrotoxin (8 mg/kg) seizures in male mice. The same doses of caerulein inhibited 3H-flunitrazepam binding in in vivo experiments. Proglumide, an antagonist of cholecystokinin receptors, in low dose (5 mg/kg) potentiated the effects of caerulein (100 micrograms/kg), whereas the administration of proglumide in high dose (25 mg/kg) reduced the action of caerulein on 3H-flunitrazepam binding and picrotoxin seizures. Caerulein (5-1000 nM) decreased 3H-flunitrazepam binding in in vitro experiments only after supplementation of the binding medium with 120 mM NaCl and 5mM KCl. The results suggest the possible interaction of caerulein with chloride ionophor. It seems probable that the direct interaction of caerulein with chloride ionophor in involved in the inhibitory effect of caerulein on picrotoxin seizures and 3H-flunitrazepam binding.

Topics: Animals; Brain; Ceruletide; Dose-Response Relationship, Drug; Drug Interactions; Flunitrazepam; Male; Mice; Picrotoxin; Proglumide; Reaction Time; Receptors, GABA-A; Seizures

Cholecystokinin octapeptide (CCK-8), caerulein and diazepam inhibited exploratory rearing activity and harman-induced convulsions in mice. Pretreatment with the selective benzodiazepine receptor antagonist Ro 15-1788, reduced or abolished the sedative and anticonvulsive effects of diazepam, but left the same effects of both peptides unaffected. The peptide-induced ptosis was even increased by Ro 15-1788. The results suggest that the CCK-like peptides do not directly interact with the benzodiazepine receptor.

Topics: Animals; Anticonvulsants; Benzodiazepinones; Blepharoptosis; Body Temperature; Ceruletide; Cholecystokinin; Diazepam; Flumazenil; Harmine; Hypnotics and Sedatives; Male; Mice; Peptide Fragments; Seizures; Sincalide

Caerulein, cholecystokinin octapeptide (CCK-8) and diazepam delayed the onset of seizures produced by harman and thiosemicarbazide (TSC). Caerulein had the potency of diazepam, whereas CCK-8 was less active by a factor of four. The convulsions induced by isoniazid (INH) were very resistant to both caerulein and diazepam; CCK-8 was not tested against isoniazid. Haloperidol did not influence the effect of TSC; it enhanced isoniazid-induced seizures, and antagonized the convulsant effect of harman.

Topics: Animals; Anticonvulsants; Ceruletide; Cholecystokinin; Diazepam; Haloperidol; Harmine; Isoniazid; Male; Mice; Mice, Inbred Strains; Seizures; Semicarbazides; Sincalide

Caerulein and the C-terminal octapeptide of cholecystokinin (CCK-8), after subcutaneous administration to mice, both delayed the onset and retarded the development of toxic effects of convulsants such as strychnine, pentetrazol, bicuculline, and picrotoxin. They also increased the seizure threshold doses of intravenously infused pentetrazol and picrotoxin. In this regard, both peptides were at least equipotent with diazepam.

Topics: Animals; Anticonvulsants; Bicuculline; Ceruletide; Cholecystokinin; Diazepam; Kinetics; Male; Mice; Pentylenetetrazole; Seizures; Sincalide; Strychnine; Time Factors