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J N Joyce

Publications and source records attributed to J N Joyce.

84 records · Page 5Linked to original sources
PubMed1984

Behaviors induced by intrastriatal dopamine vary independently across the estrous cycle.

Unilateral intrastriatal injections of dopamine (DA; 25 micrograms/0.25 microliters) or amphetamine ( AMPHET ; 25 micrograms/0.25 microliters) induced contralateral postural deviation and contralateral rotation that varied systematically across the estrous cycle of Long-Evans hooded rats. Both the deviation and rotation elicited by either drug were suppressed during the early part of the day of proestrus (2-6 hours after lights on) and were enhanced on the day of estrus, compared to the other days of the estrous cycle. However, when the behaviors elicited by the two drugs were examined across the day of proestrus, it was found that postural deviation and rotation changed independently. Postural deviation elicited by intrastriatal DA and AMPHET was suppressed on the day of proestrus at 4 and 7 hours after lights on, but was enhanced to the level seen during estrus at 11 hours after lights on. In contrast, contralateral rotation induced by either drug was suppressed 4, 7 and 11 hours after lights on and was enhanced only by the morning of estrus. These data suggest that there are separate DA-modulated mechanisms within the striatum for postural deviation and contralateral rotation, and that these mechanisms are differentially affected across the estrous cycle.

Animals↗
PubMed1984

Estradiol application to one striatum produces postural deviation to systemic apomorphine.

In order to test whether estrogen acts directly in the dorsal striatum to affect dopamine-mediated behavior, ovariectomized female Long-Evans rats were given a unilateral striatal application of estradiol, injected systemically with apomorphine (APO), and tested for lateralization of stereotypic behaviors. In the first experiment, estradiol, cholesterol, or an empty cannula was inserted and the rat given 0.7 mg/kg APO 1-4 hours later. Rats directed their stereotypic behaviors to the side ipsilateral to the insert of estradiol with dorsal striatal inserts, but not with inserts in ventral striatum or neocortex. Neither cholesterol nor the empty cannula inserts were effective in producing lateralization of the stereotypic behaviors. In the second experiment, intrastriatal inserts of 17 alpha-estradiol were ineffective in producing a lateralization of APO-induced stereotyped behavior. In the third experiment, several doses of APO (0.07, 0.75 and 3.0 mg/kg) were tested. At the highest dose no lateralization of APO-induced stereotypic behavior was observed. These results strongly suggest that estradiol acts directly in the dorsal striatum to antagonize APO and thus produce a lateralization of stereotypic behaviors (postural deviation).

Animals↗
PubMed1984

Dopamine-mediated behaviors: characteristics of modulation by estrogen.

Several behaviors produced by intrastriatal injection of dopamine (DA) and amphetamine (AMPHET) in ovariectomized (OVX) rats were each modulated by estradiol benzoate (EB) in different ways. Contralateral postural deviation and rotation, induced by unilateral injections of DA and AMPHET into the dorsal striatum, were differentially suppressed with EB treatment. Postural deviation was suppressed by 1/2 hour after a single treatment with EB (2 micrograms). In contrast, suppression of contralateral rotation required two treatments with EB separated by an interval of 48 or 96 hours, and the suppression was observed at 24 hours after the last treatment with EB. However, treatment with the antiestrogen CI-628 blocked the suppressive effects of EB on either behavior. The enhanced locomotion produced by bilateral injections of AMPHET into the ventral striatum was not suppressed with EB. In fact, AMPHET-enhanced locomotor activity decreased after a 3-week absence of estradiol as a consequence of OVX, and was returned to early OVX levels by EB. Therefore, postural deviation, rotation, and locomotor activity are mediated by different underlying mechanisms in the striatum and are affected differently by estradiol.

Amphetamine↗
PubMed1984

Rotation and postural deviation elicited by microinjections of dopamine into medial and lateral regions of dorsal striatum.

Unilateral microinjections of DA (25 micrograms/0.25 microliter) into several medial to lateral regions of the dorsal striatum of female rats produced both contralateral postural deviation and rotation. However, injections of DA into the medial striatum were more effective in producing rotation than postural deviation, whereas the opposite was the case for lateral striatal injections.

Animals↗
PubMed1983

Systemic apomorphine reverses intrastriatal dopamine-induced contralateral deviation.

Contralateral deviation induced by unilateral injection of 25 micrograms or 100 micrograms dopamine into the dorsal CPU was reversed to ipsilateral deviation by apomorphine administered systemically (1 mg/kg s.c.) before, at the same time, or after the dopamine. Contralateral deviation to a unilateral intrastriatal injection of 6.25 micrograms apomorphine was also reversed to ipsilateral deviation by systemically administered apomorphine. No significant effects on postural deviation were found when a control solution was injected unilaterally into the striatum, followed by systemic apomorphine. Contralateral deviation to the unilateral intrastriatal dopamine injection continued following a further bilateral intrastriatal injection of either dopamine or apomorphine. These results suggest that intrastriatal dopamine indirectly affects sites receptive to dopamine outside the striatum.

Animals↗
PubMed1983

Multiple dopamine receptors and behavior.

The therapeutic effects of dopamine (DA) agonists and DA antagonists used in the treatment of schizophrenia (antipsychotics, DA antagonists), Huntington's chorea (DA antagonists) and Parkinson's disease (antiparkinsonian agents, DA agonists) have been thought to result largely from actions on DA receptors located in the striatum (caudate nucleus and putamen). Many of the classical drugs used to treat these disorders are known to have a high incidence of extrapyramidal side effects (EPS). However, a number of drugs, the atypical antipsychotics and antiparkinsonian agents, have been developed which have a low incidence of EPS. It has been of enormous interest to researchers and clinicians alike to determine what characteristics of the atypical antipsychotics and antiparkinsonian agents are responsible for their unique behavioral profile. Because all of the antipsychotics and antiparkinsonian agents act on DA receptors, much attention has focused on potential differences in the interactions of the atypical agents with DA receptors. An hypothesis that has been raised, due to the knowledge that there are multiple subtypes of DA receptors located in the striatum, is that the atypical agents could have their therapeutic actions as a result of an interaction with one specific subtype of DA receptor. This review emphasizes two major points: (1) it is unlikely that the atypical antipsychotics and antiparkinsonian agents interact with only one subtype of DA receptor, or have their therapeutic actions only through that receptor; (2) other pharmacological characteristics of these agents are more critically involved in their unique behavioral effects. The applicability of animal models to assess the pharmacological and behavioral profiles of these agents is discussed, and the relevance to the clinical profiles of these agents is emphasized.

Acetylcholine↗
PubMed1982

Estradiol suppresses then enhances intracaudate dopamine-induced contralateral deviation.

The effects of estradiol on the amount of contralateral postural deviation elicited by unilateral intracaudate injection of dopamine (DA) were tested 2 days and 6 days after hormone treatment. DA (25 micrograms/0.25 microliter) or a control vehicle solution (VH, 0.25 microliter) was injected unilaterally into the dorsal anterior caudate-putamen of intact male rats and postural deviation was measured. Then, rats were given estradiol benzoate (EB, 50 micrograms/100 g body wt per 0.05 ml) or the vehicle, peanut oil (OIL, 0.05 ml/100 g body wt) once. At 2 days and 6 days after EB or OIL treatment, the rats were again administered DA or VH intrastriatally and the amount of contralateral postural deviation was measured. At 2 days after EB treatment the response to intrastriatal DA was significantly decreased, but by 6 days it was significantly increased; OIL had no effect. Thus, the behavioral effects of estrogen are time-dependent and may affect the postsynaptic response to DA in the striatum.

Animals↗
PubMed1981

Behavioral effects of unilateral dopamine injection into dorsal or ventral striatum.

Dopamine or its vehicle saline was injected unilaterally into dorsal striatum, ventral striatum, or sites outside the striatum in adult male rats. Direction, duration and frequencies of ongoing behaviors were measured. Dopamine injected into any site within the striatum immediately elicited more contralaterally directed behavior than the vehicle injected into the same site. The contralaterally directed behaviors were no longer duration when injected into the dorsal than into the ventral striatum, a result which might reflect regional differences in numbers of dopamine receptors or distribution of efferents. At the doses employed (25 and 100 microgram), dopamine injected unilaterally into the striatum did not induce rotation, stereotyped behavior, or even a significant change in the frequencies of ongoing behaviors; rather, all ongoing behaviors were expressed in a contralateral direction. Thus, the behavioral effects of dopamine in the striatum are best understood as a change in sensory-motor responsiveness.

Animals↗
PubMedDate not supplied

Limbic circuits and monoamine receptors: dissecting the effects of antipsychotics from disease processes.

There is considerable evidence for the involvement of brain dopaminergic and serotonergic systems in schizophrenia pathology. However, post-mortem studies have been limited by difficulties in separating the effects of chronic exposure to antipsychotics from that of the disease process. Our recent studies directly explored this by comparing groups that were free from antipsychotic treatment for up to a year prior to death and that were maintained on antipsychotics. We have used this approach to identify that there are prominent effects of both disease and of antipsychotic treatment. There appears to be a high association for schizophrenics between elevations of D3 receptors in target regions of the mesolimbic dopamine (DA) system and elevated numbers of 5-HT(1A) receptors in prefrontal cortex (PFc). Antipsychotic treatment was correlated with a reduction of D3 receptors in the ventral striatum and its output structures. It also led to a reduction in the number of 5-HT2 receptors in some regions of the PFc without modifying the concentration of 5-HT(1A) receptors. The limbic loop interconnecting the PFc and ventral striatum may be the site of antipsychotic regulation of certain symptoms in schizophrenia, particularly anhedonia and depression. The positive symptoms of schizophrenia are more likely to be associated with disturbances in the temporal lobe. However, dopaminergic systems in the temporal lobe have historically been thought to be underdeveloped compared to that in the basal ganglia and unlikely to be the target of antipsychotics. Our studies of the expression of the DA D2 receptor in the temporal lobe has shown a complex organization in the perirhinal and temporal cortices that is disrupted in schizophrenia. The disturbances, which might be of neurodevelopmental origin and are unrelated to antipsychotic treatment, include altered laminar distribution of the D2 receptor and modified modular organization of D2 receptors in the superior temporal gyrus. We hypothesize that modified expression of D2 receptors in these regions play a key role in the genesis of hallucinations. Treatment with antipsychotics leading to D2 receptor blockade in temporal cortex may reduce the presence of positive symptoms.

Antipsychotic Agents↗
PubMedDate not supplied

Dopamine D3 receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs.

The cloning of the gene for the D3 receptor and subsequent identification of its distribution in brain and pharmacology allowed for serious consideration of the possibility that it might be a target for drugs used to treat schizophrenia and Parkinson's disease (PD). That is because it is highly expressed in limbic regions of the brain, exhibits low expression in motor divisions, and has pharmacologic similarity to the D2 receptor. Thus, antipsychotics that were presumed to block D2 receptors also had high affinity for the D3 receptor. Dopamine agonists used to treat the clinical symptoms of PD also have high affinity for the D3 receptor, and two D3 receptor-preferring agonists were found to be effective for treatment of PD. Many compounds achieving high potency and selectivity are now available, but few have reached clinical testing. Recent findings with respect to the anatomy of this receptor in human brain, altered expression in schizophrenia and PD, and biological models to study its function support the proposal that it is a target for development of drugs to alleviate symptoms in neuropsychiatric and neurologic disorders. Because of distinct aspects of regulation of the D3 receptor, it represents a unique target for therapeutic intervention in schizophrenia without high potential for unintended side effects such as tardive dyskinesia. It may also be that D3 receptor agonists can provide neuroprotective effects in PD and can modify clinical symptoms that D2 receptor-preferring agonists cannot provide.

Animals↗
PubMedDate not supplied

Timing: A critical determinant of the functional consequences of neonatal 6-OHDA lesions.

Previous data have indicated that intrastriatal (IS) lesions of the dopamine (DA) system early in development result in a selective effect on D1 receptor expression and sensitivity, which is not seen with adult lesions or lesions made later in development. The purpose of the present study was to test the hypothesis that the timing of the lesion is a critical determinant of the consequences of DA depletion during development. Rats received IS injections of 6-hydroxydopamine (6-OHDA) on day of birth/postnatal day 1 (P0/1) or P7, which resulted in similar decreases in the number of DA uptake sites (> or =70% loss), a measure of DA terminal density. As adults, lesioned rats were challenged with DA receptor agonists to examine the functional sensitivity of D1 and D2 receptors. In adulthood, P0/1-lesioned rats exhibited increases in oral dyskinesias and rearing behavior following treatment with the partial D1 receptor agonists, SKF38393 and SKF77434, whereas rats lesioned on P7 exhibited increases in grooming. P7-lesioned rats also exhibited increases in gnawing, explosive jumping, and self-biting behavior following treatment with the full D1 receptor agonist SKF82958, which were not observed in the other groups. The results support the hypothesis that the timing of DA denervation is of paramount importance for governing the functional consequences of neonatal lesions, as measured by the incidence of DA agonist-induced behaviors in adulthood.

Aging↗