Subject(s)
Behavior, Animal/drug effects , Methamphetamine/pharmacology , Neurotoxins/pharmacology , Animals , Apomorphine/pharmacology , Avoidance Learning/drug effects , Dopamine Agonists/pharmacology , Male , Methoxydimethyltryptamines/pharmacology , Motor Activity/drug effects , Rats , Rats, Wistar , Reaction Time , Retention, Psychology/drug effects , Serotonin Receptor Agonists/pharmacology , Stereotyped Behavior , Time FactorsABSTRACT
The dipeptidyl aminopeptidase IV (DP IV) inhibitor Diprotin A produces a full, dose-dependent, short-lasting and naloxone-reversible analgesia in the rat tail-flick test when given intracerebroventricularly, with an ED50 of 295 nmol/rat but it has no direct opioid agonist activity in the longitudinal muscle strip of guinea-pig ileum bioassay. Two of the potential DP IV substrates, morphiceptin and endomorphin 1, identified recently in bovine brain were also analgesic given by similar route. The action of endomorphin 1 was more potent (ED50 = 7.9 nmol/rat) and slightly but significantly more sustained than that of Diprotin A. Diprotin A neither potentiated nor prolonged the effect of a marginally analgesic dose of endomorphin 1. The distinct time course and the lack of potentiation indicate that in the analgesic effect of Diprotin A in rats the protection of a brain Tyr-Pro-peptide other than endomorphin 1 is involved.
Subject(s)
Analgesia , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/antagonists & inhibitors , Naloxone/pharmacology , Oligopeptides/pharmacology , Analgesics, Opioid/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Synergism , Endorphins/administration & dosage , Endorphins/pharmacology , Guinea Pigs , In Vitro Techniques , Male , Mice , Muscle, Smooth/drug effects , Narcotic Antagonists/pharmacology , Oligopeptides/administration & dosage , Pain Measurement , Rats , Rats, WistarABSTRACT
Effects of deprenyl and amphetamine enantiomers on different behavioural patterns were compared. Whereas (+)-amphetamine in doses of 1-3 mg/kg SC, (-)-amphetamine, and (+)-deprenyl in doses of 5-20 mg/kg SC increased the locomotor activity and the time the animals displayed stereotyped head movement, enhanced the acquisition of conditioned avoidance responses, and developed positive place preference conditioning, (-)-deprenyl, even in as high a dose as 20 mg/kg SC, failed to show any amphetamine-type behavioural effect. The results provide further proof why (-)-deprenyl, in contrast to other members of the amphetamine family, can be considered as a safe drug.
Subject(s)
Amphetamine/pharmacology , Behavior, Animal/drug effects , Central Nervous System Stimulants/pharmacology , Monoamine Oxidase Inhibitors/pharmacology , Selegiline/pharmacology , Animals , Avoidance Learning/drug effects , Conditioning, Operant/drug effects , Female , Head Movements/drug effects , Male , Motor Activity/drug effects , Rats , Rats, Wistar , Stereoisomerism , Stereotyped Behavior/drug effectsABSTRACT
The selective monaminooxidase (MAO)-B inhibitor (-)deprenyl facilitates the nigrostriatal dopamine (DA)-ergic system by a complex mechanism that includes inhibition of DA reuptake and increase of DA turnover. In this study, DA reuptake and DA turnover were measured in the olfactory tubercle of rats treated with 0.25 mg/kg (-)deprenyl for 28 days. There was no difference between these rats and the saline-treated group. In another series of experiments, we analysed how (-)deprenyl influences the action of some indirectly acting DA agonists, such as amphetamine (AM) and phenylethylamine (PEA). The effect on different behavioural patterns related either to the nigrostriatal (stereotyped behaviour) or the mesolimbic (rearing, locomotion) DAergic system was investigated. As expected, the PEA-induced stereotyped behaviour was tremendously potentiated by (-)deprenyl and the AM-induced stereotypy was reduced. At the same time there was no change in locomotion and rearing. The results give further biochemical and behavioural proof that (-)deprenyl enhances the function of the nigrostriatal DAergic system and leaves the mesolimbic DAergic neurons unaffected.
Subject(s)
Dopamine/physiology , Limbic System/physiology , Selegiline/pharmacology , Amphetamine/pharmacology , Animals , Cell-Free System/drug effects , Cell-Free System/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine/metabolism , Female , Limbic System/drug effects , Limbic System/metabolism , Male , Motor Activity/drug effects , Olfactory Bulb/drug effects , Olfactory Bulb/metabolism , Phenethylamines/pharmacology , Rats , Rats, Wistar , Stereotyped Behavior/drug effectsABSTRACT
Dopamine (DA) insufficiency in the ipsilateral corpus striatum produced by unilateral electrolytic lesion of the substantia nigra (SN) resulted in an impairment in rats' behavior as tested by one-way and two-way avoidance techniques. Selective MAO-A inhibitor, clorgyline (1 mg/kg sc daily for 7 days), improved the reduced learning capacity of SN lesioned animals, restored the decreased DA content in the corpus striatum, and caused significant hyperactivity as tested in the open field. At the same time the selective MAO-B inhibitor (-)deprenyl (injected the same way) proved to be ineffective. J-508, a selective MAO-B inhibitor, used in a non-selective dose (1 mg/kg), acted like clorgyline. The results support the hypothesis that in the rat nigrostriated system (but not in human beings) DA is preferentially deaminated by the A form of MAO.
Subject(s)
Avoidance Learning/drug effects , Monoamine Oxidase Inhibitors/pharmacology , Animals , Clorgyline/pharmacology , Corpus Striatum/metabolism , Male , Motor Activity/drug effects , Rats , Selegiline/pharmacology , Substantia Nigra/physiology , Time FactorsABSTRACT
Behavioral and biochemical effects of 1-deprenyl and clorgyline were studied in Wistar rats. Behavioral performances was tested in a one-way and in a two-way avoidance system. The two MAO inhibitors were given acutely (1 and 10 mg/kg sc) anc chronically (1 mg/kg sc/daily, for 7 days), and their influences on learning and retention performance was tested 24 hr after the last injection. Behavioral reactions remained unchanged after acute administration of the inhibitors, while they were significantly improved following the chronic treatments, either in the one-way or in the two-way experimental situation. Biochemical analysis indicated dissociation between the influence on striatal dopamine content and the behavioral effects of 1-deprenyl and clorgyline.
