Conditioning of morphine-induced locomotor activity and stereotyped behaviour in rats. 1989

S Walter, and K Kuschinsky
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Federal Republic of Germany.

Morphine (15 mg/kg i.p.) produces a biphasic effect: hypokinesia, followed by hyperkinesia and stereotyped behaviour. After repeated administration, the signs of the second phase more and more predominate. In the following study, it was evaluated, to which degree "classical" pharmacodynamic tolerance to hypokinesia or, alternatively, conditioning phenomena contribute to this shift. In particular, it was studied whether not only hyperkinesia but also stereotypies could occur as conditioned responses either in the presence or in absence of morphine. Rats were conditioned 8 times with morphine (15 mg/kg i.p.) in the presence of various, defined conditioned stimuli (auditory, olfactory and tactile), another group was "pseudoconditioned", i.e. they were exposed to the same treatment schedule of morphine and stimuli, but with no positive association between drug and stimuli, a third group ("naive rats") was treated with saline instead of morphine, but exposed to the same stimuli as both other groups. All groups were tested for conditioned responses in the presence of the conditioned stimuli. One series of experiments was performed with saline after a break of 2 days after the end of the conditioning period, a second series was tested with saline after a break of 7 days, a third series with morphine (15 mg/kg i.p.) after a break of 2 days, a fourth series with the same dose of morphine after a break of 7 days. The results showed that when morphine was used after a break of 2 days, "classical" pharmacodynamic tolerance, but not conditioning phenomena could explain the shift in behaviour, whereas under the three other protocols described, some conditioned behavioural effects could be observed, either in presence or in absence of morphine, at least in part of the parameters used (locomotor activation, decrease in hypokinesia, sniffing, gnawing, rearing, but not in licking). Accordingly, development of pharmacodynamic tolerance and, to a lesser degree, conditioning contribute to the shift in behaviour after repeated administration of morphine. The conditioned effects could not be attributed to any alteration in striatal or mesolimbic dopamine turnover.

UI MeSH Term Description Entries
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003214 Conditioning, Classical Learning that takes place when a conditioned stimulus is paired with an unconditioned stimulus. Reflex, Conditioned,Classical Conditioning,Classical Conditionings,Conditioned Reflex,Conditionings, Classical
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013239 Stereotyped Behavior Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive. Behavior, Stereotyped,Behaviors, Stereotyped,Stereotyped Behaviors
D015102 3,4-Dihydroxyphenylacetic Acid A deaminated metabolite of LEVODOPA. DOPAC,Homoprotocatechuic Acid,3,4-Dihydroxyphenylacetic Acid, Monosodium Salt,3,4 Dihydroxyphenylacetic Acid

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