Effects of apomorphine on free-operant avoidance behavior in the rat

doi:10.1016/0014-2999(68)90070-8

European Journal of Pharmacology

Volume 3, Issue 2, May 1968, Pages 163-166

https://doi.org/10.1016/0014-2999(68)90070-8 Get rights and content

Abstract

Injection of apomorphine 0.4–1.6 mg/kg had a differential effect on free-operant avoidance behavior in rats. One group of animals showed an increase in lever-pressing rate accompanied by a decrease in shock frequency. The opposite relationship was observed in another group. Apomorphine elicited sterotyped movements in both groups.

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Evidence for dopamine receptor stimulation by apomorphine
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Relation between the action of dopamine and apomorphine and their O-methylated derivatives upon the CNS
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Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats
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Site of action of dopamine and apomorphine on compulsive gnawing behavior in rats
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Cited by (16)

Effects of apomorphine on escape performance and activity in developing rat pups treated with 6-hydroxydopamine (6-OHDA)
1980, Pharmacology Biochemistry and Behavior
The effects of apomorphine and escape learning were examined in normal developing rat pups and littermates preferentially depleted of brain dopamine by the intracisternal administration of 6-hydroxydopamine (6-OHDA) at 5 days of age, a treatment which resulted in a rapid and permanent reduction in brain dopamine to concentrations 12–29% of littermate controls while norepinephrine was not significantly altered. At 19 days of age both 0.1 and 1.0 mg/kg doses of apomorphine increased general motor activity in normal but not 6-OHDA treated pups (though these pups were significantly hyperactive prior to apomorphine). At 26 days only the 1.0 mg/kg dose increased motor activity in both normal and 6-OHDA pups. Exploratory activity at 30 days in both normal and 6-OHDA pups was first reduced then abolished by progressive doses of apomorphine. Stereotyped activity was increased by 0.1 1.0 mg/kg apomorphine at 19 days in both normal and 6-OHDA pups. By 26 days, apomorphine no longer produced intense stereotypies in normal pups, but did effect such responses in 6-OHDA treated animals. Administration of apomorphine resulted in a disruption of escape performance in a T-maze and shuttle box in normal pups only at 1.0 mg/kg but disrupted performance in 6-OHDA treated animals at both 0.1 and 1.0 mg/kg dosages. These results indicate a peak effect of apomorphine on general motor activity at three weeks of age in normal pups. Our results also suggest that apomorphine will disrupt escape learning, effects that appear to be correlated with the apomorphine induced increase in motor activity.
Pharmacology and Neurochemistry of Apomorphine
1978, Advances in Pharmacology
This chapter discusses the pharmacology and neurochemistry of apomorphine. Apomorphine was first employed as a powerful emetic agent. Apomorphine can be obtained by the acid-catalyzed rearrangement of morphine and by total synthesis. The hydrochloride forms colorless crystals that readily undergo superficial oxidation and assume a greenish tinge. Apomorphine solutions in water are unstable, turning green upon exposure to light and to air oxygen. Oxidation of apomorphine is much slower in acidic media. These properties of apomorphine explain the current addition of ascorbic acid to apomorphine solutions. The preparation of apomorphine by the acid-catalyzed rearrangement of morphine results in the retention of the configuration at the C6a chiral center leading to the corresponding (–)-isomer. Apomorphine has been measured in biological samples by spectrophotometric and fluorimetric methods and by fluorescence quenching after chromatographic separation. Apomorphine is metabolized by O-glucuronidation, O-methylation, and, probably, by N-demethylation. Apomorphine is methylated in vitro when incubated with rat liver soluble fraction in the presence of S-adenosylmethionine as methyl donor. This reaction is carried by the enzyme COMT.
Apomorphine: Chemistry, pharmacology, biochemistry
1976, International Review of Neurobiology
This chapter discusses the chemistry, pharmacology, and the biochemistry of apomorphine. Apomorphine (APO) is a tertiary base with the empirical formula C₁₇H₁₇NO₂. Its molecular skeleton consists of four fused six-membered rings, giving the molecule a semirigid structure. Its molecular skeleton is that of an aporphine alkaloid; owing to the catechol moiety in ring D, it oxidizes rapidly and becomes green on exposure to air and in solution. APO can be acetylated to diacetylapomorphine without loss of potency. However, etherification leads invariably to less active or inactive compounds. 11-Hydroxy-10-methoxyaporphine (apocodeine) and 10,11-methylenedioxyaporphine are about four times less potent than APO in inducing stereotyped gnawing in rats, while 10,11 -dimethoxyaporphine is inactive. Monohydroxy derivatives of aporphine are inactive. The N-methyl group of 10-or 11-hydroxyaporphine is replaced by a N-n-propyl substituent, some activity is retained; these compounds are nevertheless less potent than APO. It is concluded that the 10, 11-dihydroxy substitution pattern of APO is an absolute requirement for optimal activity.
Stereotyped behavior
1975, Pharmacology And Therapeutics: Part B: General And Systematic
The term ‘tereotyped behavior’ is used in psychology, psychiatry and psychopharmacology to designate rather different forms of behavior and must therefore be used with some caution to avoid misunderstanding. In the following we shall discuss the stereotyped behavior that is elicited by amphetamines and related drugs, i.e., apomorphine. This behavior is probably mediated by dopamine in the corpus striatum (see below) and is thus related to the extrapyramidal system.
Effects on precise motor responding of bilateral intrastriatal application of dopamine
1974, Behavioral Biology
Bilateral intrastriatal administration of dopamine (200 μg over 2 hr) in iproniazid-treated rats produced stereotyped movements of the jaws and forelimbs. In an experimental situation specifically designed to measure behaviorally the analog characteristics of motor responses, these rats displayed oscillatory, choreiform-like response patterns. This motor symptomatology was not observed after intrastriatal application of dopamine or noradrenaline alone, or after intracortical administration of dopamine. It was concluded that increments in striatal dopamine may be correlated with the production of chorea and related reiterative motor processes.
Effects of apomorphine on self-stimulation
1973, Pharmacology, Biochemistry and Behavior
In rats, self-stimulation (SS) from posterior lateral hypothalamus and ventromedial tegmentum was suppressed by the ip administration of alpha-methyl-para-tyrosine methyl ester (α-MPT, 100 mg/kg). Apomorphine (0.25 or 0.5 mg/kg) was injected ip $312 hr$ after α-MPT treatment. Self-stimulation was reinstated to a significant degree, after 2 hr for the 0.25 mg/kg group, and 3 hr for the 0.5 mg/kg group. Apomorphine given after saline control, elicited an immediate suppression of SS for approximately $12 hr$ in the case of 0.25 mg/kg and $112 hr$ for 0.5 mg/kg.

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Short communicationEffects of apomorphine on free-operant avoidance behavior in the rat

Abstract

Evidence for dopamine receptor stimulation by apomorphine

J. Pharm. Pharmacol.

Relation between the action of dopamine and apomorphine and their O-methylated derivatives upon the CNS

Psychopharmacologia

Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats

Psychopharmacologia

Site of action of dopamine and apomorphine on compulsive gnawing behavior in rats

Experientia

Short communication
Effects of apomorphine on free-operant avoidance behavior in the rat