Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Apomorphine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources

Chronic administration of haloperidol during development: later psychopharmacological responses to apomorphine and arecoline.

Offspring of pregnant rats injected with 0.25 mg/kg of haloperidol or saline throughout gestation and until weaning were psychopharmacologically tested for their responsiveness to arecoline and apomorphine. On postnatal day 50, offspring of such chronic treatments were tested in the open field after administration of 0, 0.05, 0.1, 1.0 or 3.0 mg/kg apomorphine, a dopamine agonist. The two chronic treatment groups did not differ in response to high doses of apomorphine which induced stereotyped sniffing and a depression of matrix crossing behavior. However, while control offspring exhibited a low dose (0.05 mg/kg apomorphine) suppression of matrix crossings and rearing behavior, haloperidol treated offspring did not, which may indicate a functional hyposensitivity of dopaminergic autoreceptors in these treated animals. When tested at postnatal day 65 for their cataleptic responses to the cholinergic agonist arecoline, haloperidol treated offspring were more cataleptic to 2 and 5 mg/kg arecoline than control offspring. This suggests that chronic dopamine receptor blockade during development may have long-term indirect effects on the sensitivity of the cholinergic system.

Animals↗

Circadian rhythm of apomorphine-induced stereotypy in rats.

The existence of circadian variations of apomorphine-induced stereotypy was determined. Male Wistar rats, standardized to a light-dark cycle (lights on from 7:00--19:00) for three weeks, were injected with apomorphine hydrochloride (1 mg/kg or 3 mg/kg) at one of six times (9:00, 13:00, 17:00, 21:00, 1:00 and 5:00). A significant time-of-day effect was found for apomorphine-induced stereotypy, with highest stereotypic score following injection at 13:00 or 17:00. The circadian rhythm of apomorphine-induced stereotypy was significantly fitted to a single cosine curve with a 24-hr cycle using the least squares method.

Animals↗

Apomorphine: effects on the timing and sequencing of pecking behavior in chicks.

Stereotyped behavior induced by apomorphine is thought to be "autistic", that is, impervious to environmental influence. This assumption is tested by analyzing the patterning of pecks at two differently colored stimuli in three-day old chicks treated with either 0.3 mg-kg-1 or 0.4 mg-kg-1 apomorphine. While normal chicks strongly prefer one stimulus over the other, apomorphine appears to render the choice behavior of chicks insensitive to differences between the stimuli. This result might suggest that apomorphine-treated chicks no longer perceive differences between the stimuli, but an analysis of the timing of pecks reveals that differences are still perceived since the two stimuli elicit different rates of pecking.

Animals↗

Different dopaminergic mechanisms for amfonelic acid, amphetamine and apomorphine.

Rats were trained to discriminate between the stimulus properties of intraperitoneal 0.16 mg/kg apomorphine and saline in a two-lever, food-motivated operant task. Employing the selected lever and the extended schedule performance measurements to indicate the generalization effect and perseverance of that effect, respectively, neither d-amphetamine nor amfonelic acid produced apomorphine-like discriminative properties. In contrast, administration of 0.1 or 0.2 mg/kg n-propylnoraporphine was observed to produce responses and perseverance on the apomorphine-appropriate lever that was similar to that seen after 0.16 mg/kg administration. The results of this behavioral experimentation are consistent with the notion that d-amphetamine, amfonelic acid and apomorphine may produce their dopaminergic effects by different mechanisms of action and the possibility of two sites of action for n-propylnoraporphine is discussed.

Amphetamine↗

The effect of drugs altering striatal dopamine levels on apomorphine induced stereotypy.

Drugs that increase or decrease striatal dopamine levels appear to affect apomorphine induced stereotypy. This finding was unexpected, as it has previously been maintained that drugs which exert any action on striatal DA terminals exclusively would affect only indirect dopaminergic agonists, as opposed to apomorphine which induces stereotypy by acting directly on postsynaptic dopamine receptors. Specifically, inhibiting intrastriatal dopamine levels inhibits this behavior. This effect is explained in terms of apomorphine having a greater intrinsic activity and agonist affinity for striatal dopamine receptors than dopamine itself. Thus, dopamine and drugs which promote its release, may diminish the central behavioral effects induced by apomorphine relative to drugs which inhibit dopamine release centrally.

Animals↗

Rate dependent inhibition of self-stimulation by apomorphine.

The effect of three doses of apomorphine 0.125, 0.25 and 0.5 were studied on self-stimulation generated by three levels of current intensity. Eight rats exhibited overall dose dependent decreases in self-stimulation obtained at the two lowest current intensities. Self-stimulation at the highest current intensity, however, was unaffected by even the highest dose level of apomorphine (0.5 mg/kg) despite typical signs of stereotypy exhibited by the rats in their home cages. Additionally, self-stimulation obtained under the 0.5 mg/kg dose of apomorphine under went extinction when reinforcement was discontinued. Thus, brain stimulation can be an effective reinforcement when an animal is given a stereotypy inducing dose of apomorphine if the current intensity is of sufficient magnitude and if the response manipulandum is not compatible with stereotypic responses. These observations appear consistent with a dopaminergic involvement in the response rather than reinforcement aspect of self-stimulation.

Animals↗

Hypophysectomy-induced striatal hypersensitivity and mesolimbic hyposensitivity to apomorphine.

Seven days post-hypophysectomy female rats display a hyposensitivity to the locomotor effects of apomorphine and a hypersensitivity to the stereotypy effects of apomorphine, while at 28 days post-hypophysectomy they are hypersensitive to both the locomotor and stereotypy effects of apomorphine. The hyposensitivity to the locomotor effects, at 7 days post-hypophysectomy, was associated with a decrease in 3H-spiroperidol binding and an increase in tyrosine hydroxylase activity in the nucleus accumbens septi, whereas the hypersensitivity, at 28 days post-hypophysectomy, was associated with an increase in 3H-spiroperidol and a decrease in tyrosine hydroxylase activity in the n. accumbens septi. The increased apomorphine-induced stereotypy in both the 7 and 28 days post-hypophysectomized animals was related to an increased 3H-spiroperidol binding and a decreased tyrosine hydroxylase activity in the striatum. These behavioral and neurochemical data demonstrate that following hypophysectomy female rats will develop a transient decrease in dopamine receptor sensitivity in the n. accumbens septi, while the dopamine sensitivity in the striatum is increased. Thus the hypophysectomized female rat may prove to be a valuable model to study these two separate dopamine systems and their possible modulatory roles in the display of various behaviors.

Animals↗

Pharmacologically specific pretreatment effects on apomorphine-mediated conditioned taste aversions in rats.

Pretreatment with pimozide (0.2-1.2 mg/kg) reduced a conditioned taste aversion produced by apomorphine (0.4 mg/kg) in a dose-related manner. This pretreatment effect was pharmacologically specific as shown by the inability of pimozide to prevent a conditioned taste aversion produced by nicotine (0.4 mg/kg). The results argue against the hypothesis that "proximal pre-exposure" effects are always non-specific and indicate that further pharmacological characterisation of drug-induced conditioned taste aversion may be possible. Pretreatment with a peripherally-acting antiemetic compound, domperidone, did not prevent apomorphine producing conditioned taste aversions. These data suggest that conditioned taste aversions produced by apomorphine are mediated through central dopamine receptors unrelated to the emetic properties of apomorphine and are not a result of conditioned nausea.

Animals↗

The effects of apomorphine on leverpress shock escape learning in rats.

Four groups of rats (n = 10 each) were tested on a discrete trial leverpress shock escape task 15 min following an intraperitoneal injection of either 0 (saline), 0.5, 1.0, or 2.0 mg/kg apomorphine hydrochloride. The results indicated that all doses of apomorphine produced a severe disruption in escape performance. This disruption was temporary, however, as all apomorphine groups were responding as quickly as the saline control rats by the end of the training session. A comparison of the effects of apomorphine with the previously reported effects of scopolamine and septal lesions on shock escape learning revealed both similarities and differences. These findings suggest that a septal lesion-induced reduction of acetylcholine levels does not simply "unleash" an antagonistic dopaminergic system.

Acetylcholine↗

Norepinephrine-mediated suppression of apomorphine-induced aggression and locomotor activity in the rat amygdala.

The effect of injections of norepinephrine (NE)-depleting toxin DSP-4 into the central amygdala (AMY) on apomorphine-induced fighting (AIF) was studied. In addition, the influence of such treatment on related parameters such as spontaneous activity, pain sensitivity and changes in locomotion after (+)3-PPP or apomorphine (1 mg/kg SC each) were verified. Finally, injections of NE or phenylephrine into the AMY five min before AIF were performed. DSP-4 induced marked (-71%) and selective fall in NE within the AMY accompanied by significant increase in aggressive response to 5 mg/kg of apomorphine. DSP-4-treated animals were less active in the open field and more sensitive to pain in a hot plate test. They were also more responsive to locomotor-augmenting action of apomorphine. Significant suppression of AIF was seen after injections of NE and phenylephrine into the AMY. The results suggest that NE input to the AMY plays an inhibitory role in dopamine-related locomotion and aggressivity. Moreover, amygdalar NE appears to be involved in general activity and pain perception modulation.

Aggression↗

Monosodium glutamate does not alter ACTH- or apomorphine-induced penile erection and yawning.

The effect of the intracerebroventricular (ICV) injection of ACTH 1-24 (1, 5 and 10 micrograms) or the subcutaneous administration of apomorphine (20 and 80 micrograms/kg SC) on spontaneous penile erection and yawning was studied in rats treated with monosodium glutamate (MSG), a treatment that depletes hypothalamic ACTH, alpha-MSH and endorphin-like peptides. Neonatal MSG treatment failed to antagonize either apomorphine- or ACTH-induced yawning in male and female rats, or to alter the number of penile erection episodes induced by the two substances in male rats. In contrast, hypophysectomy, that does not alter the concentration of hypothalamic ACTH and alpha-MSH, caused a marked prevention of apomorphine- and ACTH-induced responses, in agreement with previous studies. The results suggest that the integrity of opiomelanotropinergic neurons in the hypothalamus is not necessary for the induction of yawning and penile erection by ACTH-derived peptides, and that apomorphine and other dopamine agonists apparently do not induce penile erection and yawning by releasing an ACTH-derived peptide in brain.

Adrenocorticotropic Hormone↗

LHRH antagonizes yawning and genital grooming induced by apomorphine in rats.

The effects of the pretreatment with LHRH on the behavioral effects induced by low doses of apomorphine were studied in male rats. Three doses of apomorphine (31.25, 62.50 and 125 micrograms/kg) were subcutaneously administered two hours after LHRH 100 micrograms/kg or solvent SC treatment. Apomorphine induced repeated episodes of yawning and genital grooming. Pretreatment with LHRH abolished or reduced yawning and genital grooming induced by the three doses of apomorphine, suggesting that the peptide could induce subsensitivity of DA receptors responsible for yawning and genital grooming.

Animals↗

A classical genetic analysis of two apomorphine-induced behaviors in the mouse.

Apomorphine (3 mg/kg) produced in C57BL/6 (C57) mice a clear-cut increase in locomotor activity and climbing behavior in comparison with saline, while in DBA/2 (DBA) mice it produced a clear-cut decrease in locomotion and a small reduction in climbing behavior. Genetic analysis involving F1 and F2 hybrids and the backcross populations (F1 X C57; F1 X DBA) indicated that apomorphine-induced locomotion and climbing are inherited through different modes of inheritance. With regard to climbing behavior the mean analysis of apomorphine parameters showed that the additive-dominance model fitted adequately, while this single model did not fit the locomotor activity data for which the best fitting model involved epistatic parameter. Moreover, a zero correlation between the two behaviors in the F2 generation resulted, indicating that no relationship exists between these apomorphine-induced behaviors under our experimental conditions. These results suggest that the horizontal locomotion and climbing are distinct behaviors controlled, at least in part, by different genetic factors related to different dopaminergic mechanisms.

Animals↗

Apomorphine stimulation of male copulatory behavior is prevented by the oxytocin antagonist d(CH2)5 Tyr(Me)-Orn8-vasotocin in rats.

The effect of the intracerebroventricular (ICV) injection of the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin on the stimulation of copulatory behavior induced by the dopamine (DA) agonist apomorphine was studied in male rats. Apomorphine (80 micrograms/kg SC) given 5 min before mating tests decreased intromission frequency and ejaculation latency in experienced male rats. Such effects were abolished and reversed by pretreatment with 50 and 1000 ng of the oxytocin antagonist given ICV 5 min before apomorphine. The peptide per se markedly increased intromission and ejaculation latency and abolished ejaculation in control rats. The results suggest that brain oxytocin is implicated in the expression of sexual behavior, and apomorphine might improve male copulatory behavior by releasing oxytocin in brain.

Animals↗

Comparative study of the behavioral changes evoked by d-amphetamine and apomorphine in adult cats. Dose-response relationship.

The behavioral effects of d-amphetamine and apomorphine administration were studied in 17 adult cats. The doses of amphetamine administered were 0.1, 0.5, 1.0 and 5.0 mg/kg; those of apomorphine, 0.1, 0.5, 1.0 and 2.0 mg/kg. These two drugs evoked in the same animal marked differences in behavioral responses. Amphetamine induced a dose-dependent hypomotility, which was marked with the higher doses. In addition, rhythmic, bilateral slow movements of the head as a mode of stereotypy, indifference to the environment and dose-dependent increase in respiratory rate. Apomorphine elicited limb flicking, dose-dependent hypermotility and increase in olfactory behavior, the last two reactions with stereotypy characteristics. The animals appeared as if being scared, hyperreacting to sudden stimuli and showing total indifference to the surrounding environment. There were marked differences in behavioral responses evoked by these two agonists of the catecholaminergic system. These data do not conform with the behavioral reactions reported in the rat by other investigators. The disagreement with other communications is probably due to differences in reactivity of the species employed. The processes involved in the diversity of the behavioral responses of the cat to the administration of amphetamine and apomorphine have not been delucidated.

Animals↗

Apomorphine-induced flavor-drug associations: a dose-response analysis by the taste reactivity test and the conditioned taste avoidance test.

Apomorphine is a positively reinforcing drug at low to moderate doses, but appears to lose its reinforcing properties at higher doses. In Experiment 1, across a range of doses (0.5-15.0 mg/kg, intraperitoneally), apomorphine produced a CTA over 5 conditioning/testing trials which was not dose-dependent by a single bottle test. The rejection taste reactivity responses of chin rubbing and gaping, however, only occurred at the highest dose of apomorphine (15 mg/kg). In Experiment 2, a CTA test which was designed to more effectively discriminate among the different drug dose conditions indicated that the doses of 2.5, 7.5 and 15 mg/kg of apomorphine produce CTAs of equivalent strength. Our results support the contention that CTAs produced by positively reinforcing drugs are not accompanied by a palatability shift.

Animals↗

Alpha-methyltyrosine blocks the expression of rotation classically conditioned with apomorphine.

Rats with unilateral 6-hydroxydopamine lesions of substantia nigra rotate (circle) when placed, undrugged, in the environment in which they have previously been treated with apomorphine. This conditioned rotation, like the unconditioned rotation which acutely follows the administration of apomorphine, is directed away from the side with the lesion, i.e., the rotation is contralateral. Here, rats that had been administered apomorphine weeks earlier were tested, in a crossover design, for the expression of conditioned rotation following treatment with saline and with alpha-methyltyrosine. When administered four hours prior to testing, 100 mg/kg alpha-methyltyrosine significantly antagonized the expression of classically conditioned rotation. In a second group of animals, alpha-methyltyrosine had no effect on the unconditioned rotation induced by 0.05 mg/kg apomorphine.

Animals↗

A comparative study of the behavioral effects of d-amphetamine and apomorphine in the rat.

A wide range of doses of d-amphetamine and apomorphine were injected into rats, in order to better characterize and compare dopaminergic agonist-induced behavioral effects. The study was carried out using a computerized technique for the quantification and analysis of various behavioral elements. Although both drugs increased motor activity and provided dose-dependent stereotyped responses, the whole pattern of behavior in the open field showed a different structure. d-Amphetamine in doses that did not produce stereotyped responses induced a wide range of varied behavioral elements with increased frequency but decreased mean duration, while apomorphine induced a more restricted behavioral profile. Furthermore, a higher frequency of freezing reaction was observed after d-amphetamine treatment in low doses but not after apomorphine treatment. Both drugs in high doses elicited a similar stereotyped syndrome characterized by repetitive movements of great duration, but at low doses the behavioral pattern was completely different. The apomorphine-induced syndrome was characterized mainly by moving and sniffing, interrupted by rearing, while the amphetamine-induced syndrome by sniffing and moving, interrupted by standing and freezing.

Animals↗