Ability Of Apomorphine Research Articles

Ability of apomorphine and lithium chloride to create food aversions in cattle

Lithium chloride is the most common emetic used to create food aversions in laboratory animals and livestock. However, it is slowly excreted or metabolized, and requires several days for animals to recover. Because of its caustic nature and the large quantities required by cattle and sheep, lithium is best administered directly into the rumen and diluted by rumen fluid. The objective of this study was to evaluate apomorphine as an alternative emetic to create food aversions in cattle. A pilot study showed doses of apomorphine at 0.2 mg/kg BW caused some discomfort in cattle. Doses of 0.4 mg/kg BW and above resulted in severe intoxication and excessive discomfort. We then compared intramuscular injection of apomorphine at 0.1 and 0.2 mg/kg BW, to the standard dose of lithium chloride (200 mg/kg BW by gavage), and to a control treatment (200 ml water by gavage). Four heifers (428 kg) were randomly placed in each group. The heifers consumed flavored alfalfa pellets for 5 min, then were restrained in a chute and administered the respective treatment. The strength and longevity of the aversion was tested by offering the flavored pellets in single-choice extinction trials for six days. The Lithium group did not consume any flavored pellets, thus maintaining a total aversion. Both apomorphine groups reduced consumption to 40% of baseline intake, but the aversion extinguished by the end of the trial. There was no difference between the two apomorphine doses. Under these conditions, lithium chloride is superior to apomorphine in creating and maintaining taste aversions in cattle.

Changes in apomorphine pharmacodynamics following repeated treatment in 6-hydroxydopamine-lesioned rats

Rats with 6-OHDA lesions were repeatedly treated with apomorphine and dose-response relationships compared before and after treatment to better understand the pharmacological mechanisms which result in sensitization. A progressive increase in the magnitude and duration of rotational behavior was observed following repeated treatment and was associated with a nonparallel (upward) shift in apomorphine dose-response curves. These changes are inconsistent with simple shifts in drug potency, and instead are more consistent with changes in the ability of apomorphine to stimulate postsynaptic, striatal efferent pathways which result from repeated drug administration.

Age-related changes in apomorphine-induced erections

Advancing age produces a noticeable and well-documented decline in erectile function in humans. The effects of aging on the ability of apomorphine to stimulate erection and yawning behavior in rats was studied in our bioassay for potency. At the age of seven months, rats failed to respond to the same dose of apomorphine which, just one month earlier, produced erections. Erectile function was then tested in thirty-two seven-month-old rats naive to apomorphine injections, and these rats also failed to respond. Experimentally naive rats of six months of age were then tested and apomorphine produced reliable erections. It is felt that an alteration in dopamine autoreceptor function may be occurring in the central nervous system of rats at approximately seven months of age rendering them incapable of responding to apomorphine with penile erections.

Differential effects of chronic ethanol on apomorphine-induced locomotion, climbing and aggression in rats

Male Wistar rats were tested for apomorphine-induced locomotion, climbing and aggression after 3 week's intragastric ethanol (EtOH) treatment, 5 g/kg as 20% solution daily. The ability of apomorphine (APO) to elicit rearing (1 mg/kg i.p.) and climbing (0.5 mg/kg i.p.) was significantly suppressed in EtOH withdrawn animals. General locomotor activity in response to 1 mg/kg of APO i.p. did not differ between control and EtOH-treated groups. Affective aggression was checked in pairs of low-aggressive rats, i.e. resistant to the aggression inducing action of 10 mg/kg APO. No symptoms of aggression appeared in control animals whereas EtOH administered rats responded with marked aggression to APO. The different effect of chronic EtOH on responsiveness to APO in three behavioral models is discussed in terms of varying involvement of dopaminergic systems and receptors in behavioral phenomena as well as their susceptibility to prolonged EtOH.

Alterations in peripheral and central dopamine receptor sensitivity after subchronic treatment with fluphenazine and sulpiride.

The effects of subchronic treatment with the antipsychotic drugs fluphenazine and sulpiride on the sensitivity of peripheral neuronal dopamine receptors and central dopamine autoreceptors were evaluated. The ability of apomorphine, a dopamine agonist, to inhibit electrically induced sympathetic vasoconstriction in pithed rats, and apomorphine-induced inhibition of spontaneous locomotor activity in awake rats were used as indices of peripheral and central dopamine receptor sensitivity, respectively. A single injection of fluphenazine decanoate, a long-acting preparation of fluphenazine, enhanced the central locomotor inhibitory effect of low doses of apomorphine 4 and 6 weeks after drug administration, whereas the antidopaminergic effect on peripheral dopamine receptors was prolonged and persisted at least up to 6 weeks. In another set of experiments rats were treated with fluphenazine hydrochloride and sulpiride for 10 days and subsequently challenged with apomorphine after various withdrawal times. Both antipsychotic drugs augmented the inhibitory effect of apomorphine in the periphery, although the time courses of the potentiation were different. Both treatments also enhanced the locomotor inhibitory effect of apomorphine. These results are in line with our previous finding that long-term treatment with dopamine antagonists can induce neuronal dopamine receptor up-regulation also outside the central nervous system. Peripheral neuronal dopamine receptors thus show similar adaptive responses to long-term blockade as central dopamine autoreceptors, and may serve as a useful experimental model in studies concerned with mechanisms of dopaminergic autoregulation in the central nervous system.

Antagonism of apomorphine-induced yawning by SCH 23390: evidence against the autoreceptor hypothesis.

The ability of apomorphine to induce yawning (YWG) in normal and reserpinized rats and its interaction with SCH 23390, a potent and specific D-1 receptor antagonist, was studied. Apomorphine was more potent in inducing YWG in reserpine-pretreated as compared to control rats. SCH 23390, in low doses (0.05 mg/kg SC), was able to significantly reduce the YWG evoked by apomorphine both in control and in reserpine-pretreated rats. The results indicate that D-1 receptors contribute to YWG elicited by apomorphine and contradict the idea that this effect is mediated by DA autoreceptors.

Apomorphine and haloperidol effects on striatal 3H-dopamine release in anesthetized, awake restrained and freely moving rats

The ability of apomorphine (APO) and haloperidol (HAL) to affect the spontaneous release of newly synthesized 3H-DA in the striatum was studied in halothane anesthetized, gallamine paralyzed, awake restrained and freely moving rats. The striatum was continuously superfused through a push-pull cannula with a physiological medium enriched in 3H-tyrosine. Basal levels of 3H-DA release were different in the four experimental models: highest in halothane anesthetized rats, intermediate in awake restrained and gallamine treated rats and lowest in freely moving rats. In all experimental models IV or SC injection of APO (1 mg/kg) inhibited the release of 3H-DA (30–50%) from 15 to 90 min following its administration. In awake restrained and freely moving rats, stereotyped behaviour was observed for one hour following the APO injection. In halothane anesthetized rats the inhibitory effect of APO on 3H-DA release was prevented by pretreatment with HAL (2 mg/kg IV). Injection of HAL (2 mg/kg IV or SC) failed to enhance the release of 3H-DA in anesthetized and awake restrained rats, whilst a long-lasting increase in 3H-DA release was observed in gallamine treated and freely moving animals (55% and 120% respectively). However, catalepsy was observed in both restrained and freely moving rats. It is concluded that the modifications of 3H-DA release produced by HAL but not those produced by APO are dependent on the experimental model used, a fact possibly related to the different sites of action of these two drugs.

Presynaptic inhibition of dopamine synthesis in rat striatum: effects of chronic dopamine depletion and receptor blockade

These studies assessed the effects of dopamine (DA) depletion and receptor blockade on presynaptic inhibition of DA synthesis in the rat striatum. Chronic reserpine administration significantly decreased striatal DA levels but did not affect in vivo tyrosine hydroxylase activity, as determined by following dihydroxyphenylalanine (DOPA) accumulations. Both reserpine and haloperidol increased the sensitivity of presynaptic striatal DA response as determined by the ability of apomorphine (APO) to inhibit DOPA accumulation in NSD-1015-treated rats. The effect of concurrent administration of reserpine plus haloperidol on presynaptic response was additive. Additivity occurred at doses or reserpine and haloperidol while induced maximum sensitivity when administered singularly. The data suggest that increases in sensitivity of presynaptic DA response following DA depletion and receptor blockade are mediated by separate regulatory mechanisms.

A neuropharmacological analysis of central nervous system catecholamine systems in development protein malnutrition.

Four experiments were performed to evaluate the effects of developmental protein deprivation on the behavioral response of adult rats to treatments known to affect central nervous system catecholamine systems. Results showed no group differences between protein malnourished and control animals in locomotor responsiveness to d- or l-amphetamine, recovery from behavioral asymmetry produced by a unilateral lesion of the substantia nigra, or in the development of response patterns indicative of denervation supersensitivity. However, a dose-dependent diminution in the ability of apomorphine to produce stereotyped behavior was noted in the malnourished group, suggesting that a class of brain dopamine receptors may be impaired or may have undergone homeostatic modification as a result of the undernutrition procedure.