Seizure promotion and protection by D-1 and D-2 dopaminergic drugs in the mouse

Burke, K.; Chandler, Christopher J.; Starr, Beryl S.; Starr, Michael S.

doi:10.1016/0091-3057(90)90068-s

Cited by 45 publications

(24 citation statements)

References 23 publications

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“…Given that stimulation of D2 receptors prevents seizure development and allays the proconvulsant effects of DI agonists in the mouse (A1-Tajir et al, 1990a;Burke et al, 1990), we might have expected that those compounds with a poor ability to discriminate between D1 and D 2 receptors in vivo (e.g. CY 208-243 and SKF 77434), would be the least likely to lower the seizure threshold to pilocarpine.…”

Section: Discussionmentioning

confidence: 98%

“…Nevertheless, it is a moderately good seizure inducer (A1-Tajir et al, 1990a; Barone et al, 1990;Burke et al, 1990), It is possible, therefore, that full D1 agonists with improved bioavailability may not only have enhanced antiparkinson capabilities, but also induce fits more readily. It is known that small variations in the substituent groups attached to the benzazepine nucleus can markedly alter the compound's D1 binding affinity, as well as its ability to stimulate adenylyl cyclase (i.e.…”

Section: Introductionmentioning

confidence: 96%

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Seizure promotion by D1 agonists does not correlate with other dopaminergic properties

Starr

1993

J Neural Transm Gen Sect

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A range of D1 receptor agonists were tested for their ability to facilitate limbic motor seizures induced by a subthreshold dose of the chemoconvulsant pilocarpine (100 mg/kg IP) in mice. ED50 values (mumol/kg) were calculated from log dose-probit analyses, giving relative proconvulsant potencies of SKF 82958 > CY 208-243 > SKF 77434 = SKF 75670 = SKF 80723 > SKF 38393. The compound SKF 82526, which poorly crosses the blood-brain barrier, did not lower the seizure threshold. Convulsions consisted of rearing and forepaw myoclonus, leading to status epilepticus at higher doses of the D1 agonists. No deaths were recorded. A maximum seizure incidence of 50% was obtained with SKF 75670, compared to 100% for the other compounds. Apart from SKF 82526, the D1 agonists all elicited behavioural signs of central D1 receptor stimulation, including motor restlessness, grooming and sniffing. There was no obvious relationship between the abilities of these D1 agonist drugs to promote epilepsy and their effects on unconditioned motor behaviour, or their affinities and efficacies at the striatal D1 receptor. It is concluded that a reduction of the seizure threshold is an inevitable consequence of central D1 receptor stimulation with existing D1 agonists.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 96%

Seizure promotion by D1 agonists does not correlate with other dopaminergic properties

Starr

1993

J Neural Transm Gen Sect

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“…The advent of selective D, agonists with proconvulsant properties revealed for the first time that dopamine could also lower the seizure threshold from the midbrain (174). It is also known that seizures might be precipitated as a consequence of treating other neurologic disorders with D, antagonists (neuroleptics) or D, agonists (175).…”

Section: Dopamine and Epilepsymentioning

confidence: 99%

Behavioral, Psychotic, and Anxiety Disorders in Epilepsy: Etiology, Clinical Features, and Therapeutic Implications

1999

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Summary: This chapter deals with some aspects of psychiatric disturbances in people with epilepsy. Because depression and its treatment are extensively described later in this issue, they are not discussed here. The same pertains to forced normalization. Key Words: Epilepsy-Anxiety-PsychosisDepress ion-Qua1 i ty of 1 i fe-Ps e u do s ei zure s-A n t idepressants-Antipsychotics-Antiepileptic drugs.Although most people with epilepsy lead a normal emotional and cognitive life, neurobehavioral problems can be found in a large number of patients. Higher rates of psychopathology are observed in people with epilepsy relative to the general population (1,2), to other neurologic control groups (3), and to people with chronic nonneurologic disorders (1,4). In particular, increased psychopathology is more common in temporal lobe epilepsy (TLE) than in generalized epilepsy (5). Nevertheless, many issues remain highly controversial, owing in part to several methodologic problems, such as the nosographic approach, the sample examined, the type of control groups, the comparison among nonhomogeneous forms of epilepsy, and the different antiepileptic drugs (AEDs).Psychiatric disturbances can be related either to involvement of brain structures (biologic pathogenesis) or to the chronic characteristics of epilepsy (psychosocial pathogenesis). These psychiatric symptoms may develop in relationship to the seizures (in prodromal, ictal, or postictal periods) but more commonly are present in a chronic interictal condition.The wide range of clinical diversity is related to the anatomic foci, to patterns of spread, and to biologic or psychological differences among patients. Interictal behavioral changes in epilepsy remain controversial and difficult to define, mainly because pathogenesis may be attributable to several factors, such as epilepsy itself, possible brain lesions, the AEDs prescribed, and psychosocial problems (6). On the other hand, the existence of cognitive changes in epilepsy is well established, and Addrress correspondence and reprint requests to Dr. Riccardo Tom at Dipartimento di Neuroscienze, via Cherasco 11, 10126 Torino, Italy.sometimes the presence of cognitive disorders can facilitate the appearance of psychiatric disturbances (7).One of the most widely discussed problems is the incidence of psychiatric pathology in epilepsy, with a wide range of values in the literature related to the type of study. Epilepsy is characterized by a broad spectrum of severity. Ideally, patients for study trials should be selected consecutively from a general epilepsy population, but most epidemiologic studies are carried out in centers for epilepsy and include many refractory subjects who demonstrate a range of pathologic disturbances more severe than those observed in the general population of patients with epilepsy. In community studies, the prevalence of associated psychiatric disorders is low, whereas in specialty referral centers, particularly those serving indigent populations, the prevalence can rise to 25-50%: Among patient...

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“…These seizures are known to propagate through the basal ganglia, and to be highly sensitive to modulation by dopaminergic influences (A1-Tajir et al, 1990a; Burke et al, 1990;Turski et al, 1988Turski et al, , 1990. Their effects on striatal dopamine release, however, were somewhat equivocal.…”

Section: Discussionmentioning

confidence: 94%

“…In the rat pilocarpine model of human generalised convulsive epilepsy, the motor seizures induced by the cholinomimetic are sharply increased in severity by systemic pretreatment with drugs that stimulate dopamine D1 receptors or block dopamine D2 receptors, whilst the D1 antagonist SCH 23390 and D2 agonists have the opposite effect and protect animals against such seizures (A1- Tajir et al, 1990a;Starr, 1990, 1991a,b;Barone et al, 1991;Burke et al, 1990;Turski et al, 1988Turski et al, , 1990. Microinjection studies have revealed that D2-mediated influences are reproduced from the anterior compartment of the corpus striatum (A1- Tajir and Starr, 1991a,b;Turski et al, 1988), whilst the D1 drug responses can be duplicated from the midbrain substantia nigra pars reticulata (A1- Tajir et al, 1990b;Turski et al, 1990).…”

Section: Introductionmentioning

confidence: 96%

Disordered dopamine neurotransmission in the striatum of rats undergoing pilocarpine-induced generalized seizures, as revealed by microdialysis

Al-Tajir

Starr

1993

J Neural Transm Gen Sect

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In this study rats were fitted with a concentric dialysis probe in one striatum and extracellular concentrations of dopamine and HVA measured by reverse phase high performance liquid chromatography. Injections of saline or the D1 agonist SKF 38393 (30 mg/kg) did not affect the releases of these compounds. On the other hand, the D2 agonist LY 171555 (0.5 mg/kg) inhibited the release of both dopamine and HVA, whilst amphetamine (1 mg/kg) increased the output of dopamine but not HVA. Treatment with 200 mg/kg pilocarpine caused minimal signs of epileptic activity and did not affect striatal dopamine neurotransmission. Concomitant administration of SKF 38393 (30 mg/kg) to this dose of pilocarpine greatly facilitated the incidence and severity of motor seizures, which were accompanied by an irregular pattern of dopamine release and a significant rise in HVA overflow. Similar results were obtained with rats made to convulse with 400 mg/mg pilocarpine, and to a lesser extent if these animals were first pretreated with a protective dose of LY 171555 (0.5 mg/kg). It is concluded that dopamine neurotransmission in the striatum is disrupted in rats undergoing a pilocarpine-induced motor seizure, and that the extent of this disruption increases as the seizure becomes more severe. An irregular release of dopamine could signify a loss of sensorimotor control by the striatum, which might conceivably contribute to the intractability of the seizure. An increase in the dialysate concentrations of metabolite and not dopamine, is consistent with a heightened glutamate-stimulated release of dopamine from a discrete striatal pool, caused by the seizure spreading through the cortex and activating the cortico-striatal system.

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Seizure promotion and protection by D-1 and D-2 dopaminergic drugs in the mouse

Cited by 45 publications

References 23 publications

Seizure promotion by D1 agonists does not correlate with other dopaminergic properties

Seizure promotion by D1 agonists does not correlate with other dopaminergic properties

Behavioral, Psychotic, and Anxiety Disorders in Epilepsy: Etiology, Clinical Features, and Therapeutic Implications

Disordered dopamine neurotransmission in the striatum of rats undergoing pilocarpine-induced generalized seizures, as revealed by microdialysis

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