SEARCH · PubMed Health

Results for “Stereotyped Behavior”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 415 records · Page 23Linked to original sources

PubMed1988

B-HT 920 stimulates postsynaptic D2 dopamine receptors in the normal rat: electrophysiological and behavioral evidence.

The putative autoreceptor-selective dopamine (DA) agonist B-HT 920 was tested using electrophysiological and behavioral models thought to reflect actions at postsynaptic D2 DA receptors. Direct iontophoretic application of B-HT 920 onto nucleus accumbens neurons caused a current-dependent inhibition of firing which could be attenuated by pretreatment with alpha-methyl-p-tyrosine (to deplete DA) and reinstated (enabled) by concurrent administration of the selective D1 DA receptor agonist SKF 38393. These findings suggest that, like other selective D2 DA receptor agonists, the postsynaptic effects of B-HT 920 require concurrent stimulation of D1 DA receptors. Behavioral indices of postsynaptic D2 DA receptor stimulation (stereotyped sniffing and rearing) were also evident following combined treatment with B-HT 920 and SKF 38393. Moreover, similar "low-level" stereotyped behaviors were also observed when B-HT 920 was administered alone following pretreatment with the alpha-2 adrenoceptor antagonists idazoxane and piperoxane, suggesting that alpha-2 agonist actions of B-HT 920, in some way, mask the expression of D2 receptor-mediated stereotyped responses. When B-HT 920 was combined with SKF 38393 following pretreatment with idazoxane, both the intensity and form (continual licking and gnawing) of stereotyped behavior was enhanced. Taken together, these electrophysiological and behavioral findings indicate that B-HT 920 possesses the properties of a selective D2 DA receptor agonist and cannot be considered as a DA autoreceptor-selective compound.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1995

Differences between heterosexual, bisexual, and lesbian women in recalled childhood experiences.

Heterosexual, bisexual, and lesbian women recalled the extent to which they had engaged in gender conforming (female-stereotypic) behaviors and gender nonconforming (male-stereotypic) behaviors in childhood. Heterosexual women were more likely to recall having had female-stereotypic experiences as children, whereas lesbian women often recalled a childhood characterized by male-stereotypic experiences. Multiple discriminant function allowed the heterosexual women in the sample to be distinguished from the lesbian women with 80% accuracy in classification of individual cases on the basis of four recollected attributes (imagined self as a male character, wished to become a mother, preference for boys' games, and considered a tomboy as a child). However, some heterosexual women reported much the same childhood behaviors as the majority of lesbian women, and some lesbian women reported much the same childhood behaviors as the majority of heterosexual women. Such diversity raises questions about the nature of the relationship between experiences in childhood and adult sexual orientation.

Adult↗

PubMed2001

The effects of FK506, a specific calcineurin inhibitor, on methamphetamine-induced behavioral change and its sensitization in rats.

RATIONALE: FK506 inhibits calcineurin activity, resulting in the inhibition of calcium-dependent intracellular processes. Recent studies have suggested that intracellular calcium is likely to be involved in methamphetamine (MAP)-induced locomotor activity and stereotyped behavior, and in the development of sensitization to MAP. OBJECTIVES: We investigated the effects of FK506 on MAP-induced behavioral changes and the development of sensitization in rats. METHODS: In experiment 1, animals were administered IP 2 mg/kg FK506 or vehicle followed 10 min later by MAP (1, 2, 4 and 8 mg/kg, IP). Another set of animals were administered FK506 (0.1, 2, 5 and 10 mg/kg) followed by 2 mg/kg MAP. Locomotor activity and stereotyped behavior were assessed. In experiment 2, animals received repeated IP injections of 2 mg/kg MAP pretreated with 2 mg/kg FK506 or vehicle for 5 consecutive days. One week later, rats were challenged with 1 mg/kg MAP. RESULTS: Pretreatment with 2 mg/kg FK506 caused a rightward shift of the inverted U-shaped response curve of the locomotor activity induced by 1-8 mg/kg MAP. The same pretreatment significantly attenuated augmentation of the MAP-induced stereotyped behavior. FK506 at doses of 0.1-10 mg/kg dose-dependently inhibited the behavioral response induced by 2 mg/kg MAP. Coadministration of 2 mg/kg FK506 with 2 mg/kg MAP for 5 consecutive days resulted in significant suppression of the behavioral response to challenge with 1 mg/kg MAP. CONCLUSIONS: These results suggest that calcineurin plays an important role in MAP-induced behavioral changes and sensitization, especially the latter.

Animals↗

PubMed1986

Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol.

In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.

Analgesics↗

PubMed1986

Studies on the mechanism of interaction between methamphetamine and quinine in rats.

Interactions between methamphetamine and quinine were studied using two different tests. The duration and intensity of methamphetamine-induced stereotyped behavior was enhanced by pretreatment of rats with quinine. Pretreatment of rats with SKF-525A and CCl4 also resulted in the enhancement of methamphetamine-induced stereotyped behavior. Pretreatment with phenobarbital shortened the stereotypy evoked by methamphetamine. Furthermore, urinary excretion patterns of methamphetamine and its metabolites were determined following the administration of the drug to rats which had been pretreated with certain drugs. Quinine, SKF-525A and CCl4 inhibited the urinary excretion of p-hydroxylated metabolites and increased the excretion of the unchanged methamphetamine and amphetamine. These results strongly suggest that the enhancement of methamphetamine-induced stereotyped behavior in the rats pretreated with quinine, SKF-525A and CCl4 could be ascribed to the inhibition of the p-hydroxylation reaction of methamphetamine and thus may lead to the increased concentration and pharmacological effect of the drug.

Animals↗

PubMed1994

[Effects of dopamine receptor agonists and antagonists on cocaine-induced behaviors in rats].

In this study, cocaine (5-20 mg/kg), an indirect dopamine agonist, increased locomotor activity and rearing accompanied with head circling and body shaking in a dose-dependent manner. A high dose of cocaine (40 mg/kg), meaning a toxic dose, slightly induced sniffing and licking. Both SCH23390, a D-1 receptor antagonist, and raclopride, a D-2 antagonist, inhibited all behaviors induced by cocaine, suggesting that the behavioral actions of cocaine may involve the activation of D-1 and D-2 receptors. Selective D-2 agonist quinpirole (0.1 and 1.0 mg/kg) inhibited hyperlocomotion induced by cocaine (20 mg/kg), but was replaced by the typical stereotyped behaviors such as sniffing at low dose (0.1 mg/kg), and licking and gnawing at high dose (1.0 mg/kg). SK & F38393, a selective D-1 agonist, in combination of cocaine did not induce these stereotyped behaviors which resulted in synergistic interaction of D-1 and D-2 receptor stimulation. These results suggest that the indirect stimulation of postsynaptic D-2 receptors by cocaine (20 mg/kg) was insufficient to induce stereotyped behaviors. The actions of cocaine on dopamine D-1 receptors seem to be more potent than that on D-2 receptors.

Animals↗

PubMed1994

Differential involvement of voltage-dependent calcium channels in apomorphine-induced hypermotility and stereotypy.

The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive treatment (ECS). In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, inhibited the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent and ECS-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg IP that does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg IP, significantly reduced hypermotility produced by apomorphine in morphine abstinent or ECS-treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy.

Animals↗

PubMed2005

Neurobehavioral effects of tetramisole in mice.

Acute toxicity and neurobehavioral effects of the veterinary anthelmintic tetramisole were examined in male albino mice. The 24-h median lethal doses of tetramisole were determined by the up-and-down method in mice after oral, subcutaneous and intraperitoneal administrations, and they were 110, 57 and 34 mg/kg, respectively. The intoxicated mice manifested nervousness, crouching, piloerection and tremor. Subcutaneous injection of tetramisole at 0.5 and 1mg/kg did not significantly affect general locomotor activity of the mice in 5-min open-field activity test or negative geotaxis performance and landing foot splay. However, the 1mg/kg dose of tetramisole significantly increased the stereotyped behavior (grooming, sniffing, biting and licking and head bobbing) of the mice when compared to the control group. Daily treatment of mice with tetramisole at 0.5 and 1mg/kg for six consecutive days did not significantly affect their general locomotor activity in the open-field activity test. Both doses of tetramisole significantly increased stereotyped behavior of the mice on days 3, 5 and 8 in comparison with respective control values. Repeated tetramisole treatments (0.5 and 1mg/kg) also significantly decreased the time needed to complete the negative geotaxis task and reduced landing foot splay. All tetramisole-treated mice showed crouching behavior and were nervous and difficult to handle. The results suggest nervous involvement in the acute toxicity of tetramisole. Stereotyped behavior and changes in the negative geotaxis and landing foot splay are reported for the first time in mice treated with tetramisole.

Administration, Oral↗

PubMed1996

A dose-response analysis of the behavioral effects of (+)MK-801 in guinea pig: comparison with CPP.

The noncompetitive N-methyl-D-aspartate (NMDA) antagonist, dizocilpine maleate {(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine maleate} [(+)MK-801], has attracted considerable interest because of its potential use as an anticonvulsant and neuroprotectant. However, its cognitive side effects in humans have limited its use in human pharmacotherapy. Although the behavioral effects of (+)MK-801 have been documented in mouse, rat, pigeon, and rhesus monkey, there are no available data on its effects in guinea pig. The objective of this study was to conduct a dose-response analysis of the effects of (+)MK-801 on stereotyped behavior, ataxia, locomotor activity, and righting reflex latency in guinea pig. In the dose range used (0.0625-0.5 mg/kg, IP), we found no significant differences between (+)MK-801 and vehicle in terms of stereotyped behavior and locomotor activity; however, at higher doses, (+)MK-801 caused significant ataxia and impairment of the righting reflex. By comparison, the competitive NMDA receptor antagonist, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP,5 mg/kg, IP), produced neither stereotyped behavior nor impairment of the righting reflex; at higher doses (10 mg/kg, IP), it produced only ataxia and an increase in locomotor activity.

Animals↗

PubMed1989

Effect of pretreatment with amphetamine on the interaction between amphetamine and dopamine neurons in the nucleus accumbens.

The present study was designed to examine the effect of pretreatment with amphetamine on the ability of amphetamine to release dopamine from slices of the nucleus accumbens and striatum and to stimulate locomotor activity or stereotyped behavior, after direct injection into either the nucleus accumbens or the striatum. Rats were injected twice daily for 5 days with either amphetamine (5 mg/kg, i.p.) or saline. At 33 days after this pretreatment, the release of endogenous dopamine from both regions of the brain in vitro by amphetamine and the changes in behavioral responses to the direct injection of amphetamine into either region were examined. Amphetamine at both 1 and 10 microM stimulated the release of endogenous dopamine from slices prepared from both of the brain areas. The release of dopamine by amphetamine was increased in rats pretreated with amphetamine. Consistent with its ability to stimulate endogenous release of dopamine, amphetamine, when injected into the nucleus accumbens, stimulated locomotor activity, while stereotyped behavior was enhanced when amphetamine was injected into the striatum. However, the locomotor activity and stereotyped behavioral responses to small doses of amphetamine (5, 10 or 25 micrograms) were not significantly greater in amphetamine-pretreated rats, compared to saline-pretreated animals. A greater stimulation of both responses in amphetamine-pretreated rats was only observed when a large dose (50 micrograms) of amphetamine was administered into either the nucleus accumbens or striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

PubMed1997

Sequelae of parenteral domoic acid administration in rats: comparison of effects on different anatomical markers in brain.

Brain damage following administration of domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, was compared using different anatomic markers in adult rats. Seven days after administration of domoic acid (2.25 mg/kg i.p.) or vehicle, brains were collected and sectioned and stained to visualize Nissl substance using thionin, argyrophilia using a cupric silver staining method, astroglia using immunohistochemistry to detect glial fibrillary acidic protein-like immunoreactivity (GFAP-ir), and activated microglia using lectin histochemistry to detect Griffonia simplicifolia I-B4 isolectin (GSI-B4) binding in adjacent sections. In approximately 60% of rats to which it was administered, domoic acid caused stereotyped behavior within 60 min, followed by convulsions within 2-3 h. Brains of domoic acid-administered rats that did not manifest stereotyped behavior or convulsions did not differ from brains from vehicle-administered controls. In animals that had manifested stereotyped behavior and convulsions, Nissl staining was mostly unremarkable in brain sections. In contrast, there was intense argyrophilia in anterior olfactory nucleus, CA1 hippocampus, lateral septum, parietal (layer IV), piriform, and entorhinal cortices, ventral posterolateral thalamus, and amygdala. This pattern was reminiscent of that seen in postmortem specimens from humans who consumed domoic acid-tainted mussels and in experimental animals after kainic acid administration. Adjacent sections displayed astrogliosis, evidenced by increased GFAP-ir, which was more diffuse than the argyrophilic reaction. Activated microglia were revealed using GSI-B4 histochemistry. These data suggest activation of discrete brain circuits in rats that convulse following domoic acid administration and subsequent pathological alterations. The data strongly suggest that neuropathology following domoic acid occurs only in animals manifesting domoic acid-induced sterotypy and convulsions. The data do not rule out more insidious damage in behaviorally normal rats that receive domoic acid.

Animals↗

PubMed1994

Motor behavior and nigrostriatal dopaminergic activity in adult rats perinatally exposed to cannabinoids.

We have recently reported several neurochemical alterations, measured at perinatal and peripubertal ages, in the maturation of nigrostriatal dopaminergic neurons following perinatal hashish exposure. In the present work, we tried to undertake whether these neurochemical changes during ontogeny: a) were accompanied by changes of motor behavior, the main neurobiological process regulated by nigrostriatal dopaminergic neurons; and b) persisted in adulthood, leading to disturbances in the expression of an adult motor activity. To this end, two different experiments were performed. In the first, we examined, by using an actimeter, the ontogeny of spontaneous locomotor activity in immature male and female rats born from mothers perinatally exposed to hashish extract. Results showed a complete absence of significant changes in locomotor activity in females, whereas males presented a constant trend to decrease, although never statistically significant, at all ages studied as a consequence of the perinatal cannabinoid exposure. In the second experiment, we evaluated neurochemical indices--dopamine (DA) and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents, tyrosine hydroxylase (TH) activity, and number and affinity of D1 and D2 dopaminergic receptors in the striatum--and behavioral parameters--spontaneous locomotor activity and spontaneous and induced stereotypic behavior--both indicating nigrostriatal dopaminergic activity, in adult female and male rats perinatally exposed to hashish extract. Results were as follows. The spontaneous locomotor activity, measured in the actimeter, was not affected by perinatal hashish exposure in both adult males and females. This was also seen in an open-field test as measured by total number of sector crossings. However, when differentiated between internal and external sectors hashish-exposed males presented a higher number of external crossings than controls, which did not appear in females. Moreover, several induced stereotypic behaviors, such as self-grooming and shaking induced by water spraying, were also altered by hashish treatment in a sexually dimorphic manner, whereas the number of spontaneous rears and self-grooms, measured in the open-field test, was unchanged. Thus, the frequency of water spraying-induced self-grooming was significantly increased in both males and females perinatally exposed to hashish, although the increase was more marked in males (200.4%) than females (121.2%). In addition, the frequency of shaking was also markedly increased in males but remained unchanged in females. These behavioral effects were paralleled by modifications in striatal neurochemical parameters. Thus, there was a significant increase in the DOPAC/DA ratio, indicating increased presynaptic activity, in females perinatally exposed to hashish, but compensated by a lower density of D1 receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

Buspirone for stereotypic movements in elderly with cognitive impairment.

Repetitive and stereotypic behavioral disturbances in patients with dementia are common; however, little is known regarding successful treatments. The authors describe six cases of elderly cognitively impaired patients exhibiting repetitive and stereotypic behaviors who were treated successfully with buspirone. The cases demonstrate that buspirone may be an effective and safe treatment for patients with dementia who demonstrate repetitive and stereotypic behavior disorders.

Aged↗

PubMedDate not supplied

Mazindol: anorectic and behavioral effects in female rats.

The anorectic and behavioral effects of mazindol (2.5, 5 and 10 mg/kg) were determined. The experiments comprized acute and chronic administration to female rats, and the effects were compared with those produced by 2.5 mg/kg of methamphetamine. The following evaluation parameters were considered: food intake, body weight, motor activity, and stereotyped behavior. Acute administration of the three doses of mazindol, as well as of the methamphetamine dose, decreased food intake. Administered chronically to female rats, mazindol (5 and 10 mg/kg) and methamphetamine induced loss of body weight during the first fifteen days. However, weight was subsequently regained by the animals, indicating development of tolerance. Mazindol (10 mg/kg) and methamphetamine produced an increase in motor activity. This increase was, however, not observed after chronic treatment, suggesting development of tolerance. Additionally, mazindol induced noticeable dose-dependent effects, involving stereotyped behavior (sniffing, continuous licking, false bites), similar to those produced by methamphetamine. Verticalization, however, was only observed after administration of 2.5 and 5 mg/kg of mazindol, and was absent after administration of the higher dose of mazindol as well as of methamphetamine. Finally, it should be stressed that features of stereotyped behavior induced by both drugs, such as licking, false bites, sniffing and verticalization, were very similar.

Analysis of Variance↗

PubMed1980

Stereotyped behaviour in elderly patients with chronic organic mental disorder.

The presence of a variety of stereotyped behaviors was verified by observing four residents of a long-term care facility for one-hour each and recording repetitive picking, rubbing, manipulating other parts of the body, vocalizations, manipulation of objects, and sanding. It was found that at least one form of stereotyped behavior was recorded 87% of the total observation time. The overall inter-rater reliability across patients was 91%. Twenty-six patients from another long-term care facility were than randomly chosen, 13 of whom had diagnoses of cortical atrophy, and were observed for an average of 30 seconds each. A trained observer, blind to the diagnoses and to the number of such cases included in the sample, observed stereotyped behavior in and only in the 13 patients with confirmed diagnoses of cerebral dysfunction. A possible mechanism and potential clinical relevance are discussed based upon these observations.

Aged↗

PubMed1989

Synthesis and structure-activity relationship of substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones: potential anxiolytic agents.

Several novel substituted tetrahydro- and hexahydro-1,2-benzisothiazol-3-one 1,1-dioxides and thiadiazinones were prepared and examined in a series of in vitro and in vivo tests to determine their pharmacological profile. Most compounds were orally active in blocking the conditioned avoidance response (CAR) but did not antagonize apomorphine-induced stereotyped behavior. Several compounds demonstrated moderate to high affinity for the 5-HT1A receptor binding site, with compounds 37 and 38 containing 2-pyrimidinylpiperazinyl and [3-(trifluoromethyl)phenyl]piperazinyl moieties and compound 47 containing the 2-pyrazinylpiperazinyl moiety displaying the highest affinity (Ki values of 10, 4, and 9 nM, respectively). Compound 37, 3-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]hexahydro-4, 7-etheno-1H-cyclobut [f]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide, buspirone, and ipsapirone showed similarities in their neurochemical and behavioral profiles. They were similar in potency in blocking CAR with AB50 values of 39, 32, and 42 mg/kg, respectively. They also demonstrated high affinity and selectivity for the 5-HT1A receptor site (Ki = 10 nM) and exhibited partial agonist/antagonist activity in the serotonin syndrome test. In addition, compound 37 inhibited apomorphine-induced climbing behavior much more potently (ED50 of 3.4 mg/kg) than stereotyped behavior (ED50 of 32.2 mg/kg) and will be evaluated further. Structure-activity relationships within this series of compounds are discussed.

Animals↗

PubMed2005

Progesterone inhibits behavioral responses and estrogen increases corticosterone levels after acute cocaine administration.

Accumulating evidence suggests that estrogen and progesterone contribute to the sexually dimorphic behavioral response to cocaine. In this study, we tested the hypothesis that varying the level of estrogen or progesterone affects cocaine-induced locomotive behavior in female rats. Ovariectomized (OVX) rats received estrogen (0, 5, 10, 20, or 50 microg) 48 h or progesterone (0, 50, 100, 250, or 500 microg) 24 h before acute saline or cocaine (15 mg/kg) administration. Although estrogen did not affect cocaine-induced ambulatory and rearing behaviors, it affected stereotypic behaviors regardless of cocaine administration (animals receiving 50 microg had higher stereotypic counts than did the OVX group). In contrast, progesterone affected rearing activity dose-dependently: 50 and 500 microg of progesterone inhibited, whereas 100 microg and 250 microg stimulated, rearing in response to cocaine. That estrogen and progesterone did not affect overall baseline behavioral activity suggests their effects are mediated in part through interactions with cocaine. Progesterone administration did not affect corticosterone levels in saline- or cocaine-treated rats. Estrogen administration, however, affected levels of corticosterone both at baseline and after cocaine treatment. After accounting for baseline differences, we found that rats receiving 5 or 10 microg of estrogen and cocaine had higher percentage increases in serum corticosterone levels than did the control group that did not receive estrogen. On the basis of these observations, we suggest that progesterone fluctuations during the estrous cycle impact cocaine-induced behavioral responses, whereas estrogen may affect activity in the hypothalamic-pituitary-adrenal axis. Thus, dose-dependent effects of gonadal hormones may underlie some of the reported sex differences and reproductive cycle effects of cocaine.

Animals↗

PubMed1995

Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats.

Cocaine (5-40 mg/kg, intraperitoneally) enhanced locomotion and rearing accompanied with head circling and body shaking. Although at 40 mg/kg typical stereotypy licking occasionally appeared, 40% of the rats died. At doses that did not affect physiologic locomotion and rearing, the D1-receptor antagonist SCH23390 but not D2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). All behavioral responses of cocaine were abolished with increasing doses of raclopride and SCH23390. Sulpiride, a D2 antagonist, exerted a biphasic effect on locomotor activity (i.e., a low dose of sulpiride increased and a high dose decreased cocaine-induced locomotor activity). Sulpiride enhanced head circling, body shaking, and increases of rearing induced by cocaine. D2-receptor agonists quinpirole and bromocriptine inhibited these responses, presumably by activating the typical stereotyped behaviors such as sniffing at low doses, and licking and gnawing at high doses. The lowest dose of bromocriptine inhibited all behaviors induced by cocaine without producing typical stereotyped behaviors in itself. SK+F38393, a D1-receptor agonist, in combination with cocaine did not induce typical stereotype, which results in a synergistic effect of D1 and D2-receptor activities. The increases of locomotion and rearing, head circling, and body shaking induced by cocaine may involve the indirect activation of postsynaptic D1 and D2 receptors, presumably via dopamine release, resulting from inhibition of the presynaptic D2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D2 receptors by cocaine (20 mg/kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D1 receptors in mediating the behavioral actions of acute cocaine appears to be more important than that of D2 receptors. Our results also suggest that bromocriptine may be useful for the treatment of acute cocaine poisoning.

Animals↗