Dopamine D2 receptor blocking effect of imipramine in the rat hippocampus

Smiałowski, A

doi:10.1016/0091-3057(91)90404-p

Cited by 7 publications

(7 citation statements)

References 18 publications

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“…Third, there is evidence in other systems that tricyclic antidepressants can antagonize D, family dopamine receptors (Austin et al, 1991;Smialowski, 1991). In spite of this evidence, we cannot rule out the possibility that egl-2(n693) activates an octopaminergic or some other unspecified pathway.…”

Section: Analysis Of the Dominant Egl-2(n693) Mutationmentioning

confidence: 86%

“…6). A clue to the nature of such an inhibitory pathway comes from evidence that tricyclic antidepressants can antagonize D, dopamine receptors (Austin et al, 1991;Smialowski et al, 1991). Since dopamine antagonists can rescue egl-2(n693), we hypothesized that egl-2(n693) activates a negative regulatory dopaminergic pathway that can be blocked by tricyclics and D, dopamine antagonists.…”

Section: Analysis Of the Dominant Egl-2(n693) Mutationmentioning

confidence: 99%

“…Tricyclic antidepressants are used to treat a variety of human neurological disorders, but it is unclear whether their therapeutic action results from blocking 5-HT reuptake or from known nonserotonergic targets, including muscarinic, histaminergic, adrenergic (Fuller, 1987), and dopaminergic receptors (Austin et al, 1991;Smialowski, 1991). The functional significance of the molecular targets of such drugs can be studied genetically in C. elegans, though it remains to be tested how closely the action of tricyclics in nematodes parallels their action in humans.…”

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confidence: 99%

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Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans

1995

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We have investigated the neurotransmitters used to control egg-laying in C. elegans. Previous studies suggested that 5-HT released by the HSN motor neurons stimulates egg laying, and that tricyclic antidepressants potentiate egg laying by blocking reuptake of 5-HT by the HSN neurons. We report studies of the wild type and a mutant that lacks detectable 5-HT that suggest 5-HT is not required for egglaying. Furthermore, we find that ACh is required for egg laying in response to 5-HT, suggesting that 5-HT is not sufficient to activate egg laying. The dominant egl-2(n693) mutation, which causes animals to lay eggs in response to tricyclics but not 5-HT, also conflicts with the model for egg laying. Experiments in which the HSN neurons or 5-HT are removed from egl-2 animals indicate that the action of tricyclics cannot be explained by a block of 5-HT reuptake. We find that D, family dopamine antagonists can also induce egg laying in egl-2(n693) mutants, and that dopamine inhibits egg laying in the wild type. These results suggest that dominant egl-2 mutations activate an inhibitory dopaminergic pathway that can be blocked by tricyclics and D, antagonists.We also find that these drugs stimulate egg laying in mutants lacking 5-HT or the HSN neurons, consistent with a target on the egg-laying muscles. In contrast to tricyclics, fluoxetine and other selective 5-HT reuptake inhibitors appear to be specific for 5-HT reuptake in C. e/egans egg laying.[Key words: C. elegans, dopamine, egg laying, fluoxetine, genetics, HSN neurons, imipramine, pharmacology, 5HT, tricyclic antidepressant] Genetic analysis can test the validity in viva of mechanisms of synaptic transmission and can identify genes that mediate synaptic transmission. Many of the neurotransmitters found in mammals are also found in the genetic model organism Caenorhab-

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Section: Analysis Of the Dominant Egl-2(n693) Mutationmentioning

confidence: 86%

Section: Analysis Of the Dominant Egl-2(n693) Mutationmentioning

confidence: 99%

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confidence: 99%

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Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans

1995

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“…Amitriptyline is mainly classified as a neuroleptic and seems to be false-negative in this system. Imipramine has a somewhat higher neuroleptic than antidepressant score, which might be explained by its suggested effect of block ing the dopamine Dy receptor [34], Moreover, both imip ramine and amitriptyline diminish apomorphine-induced hypermotility [35] showing antidopaminergic activity. This may explain the deviating results with imipramine 132 Krijzcr/Koopraan/Olivier Psychotropic Drugs Classified by Pharmaco-ECoG and amitriptyline.…”

Section: Discussionmentioning

confidence: 99%

Classification of Psychotropic Drugs Based on Pharmaco-electrocorticographic Studies in Vigilance-Controlled Rats

1993

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The effects of a number of psycho-active drugs on electrocorticographic activity (ECoG) of the rat have been studied. Frontoparietal ECoG was recorded during 6-min periods immediately before drug/vehicle administration and starting at 20 and 45 min after administration. For each 6-min recording time, a mean power spectrum was calculated and smoothed. A quotient of the power at 20 and 45 min after and before drug, respectively, was then calculated. These quotients were used as input for an analysis of variance, followed by a t test and a normalization for the degrees of freedom, resulting in so-called n-profiles. Although each drug has its own characteristic n-profile, n-profiles of drugs belonging to the same clinical class have some characteristics in common. An automated classification system of psychotropic drugs, based on parameters extracted from n-profiles by discriminant analysis, is presented. For the antidepressant drug class the success rate of correct classification of antidepressant drugs is between 53 and 88%, for a neuroleptic drug in the neuroleptic drug class the success rate is 87%, for an anxiolytic drug in the anxiolytic drug class 100% and for a psychostimulant drug in the psycho-stimulant drug class between 86 and 100%. For a reliable classification of a drug about 10 n-profiles of active doses are needed. Using n-profiles, it appeared also possible to discriminate between antidepressant, neuroleptic, anxiolytic and psychostimulant drugs based on visual judgement. Moreover, visual evaluation of the n-profiles enables 4 subclasses to be recognized within the antidepressant class, 2 subclasses within the neuroleptic and 2 subclasses within the anxiolytic class.

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“…Moreover, chronic treatment with the antidepressant imipramine increases PSA-NCAM expression in the PCX layer II of adult rats ( Sairanen et al, 2007 ). These results are also interesting because imipramine, besides its action as a 5HT and norepinephrine reuptake inhibitor, also blocks D2 receptors ( Smiałowski, 1991 ). This is consistent with the effects that we observe with haloperidol in the present study.…”

Section: Discussionmentioning

confidence: 99%

Effects of Dopamine on the Immature Neurons of the Adult Rat Piriform Cortex

et al. 2020

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The layer II of the adult piriform cortex (PCX) contains a numerous population of immature neurons. Interestingly, in both mice and rats, most, if not all, these cells have an embryonic origin. Moreover, recent studies from our laboratory have shown that they progressively mature into typical excitatory neurons of the PCX layer II. Therefore, the adult PCX is considered a “non-canonical” neurogenic niche. These immature neurons express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a molecule critical for different neurodevelopmental processes. Dopamine (DA) is a relevant neurotransmitter in the adult CNS, which also plays important roles in neural development and adult plasticity, including the regulation of PSA-NCAM expression. In order to evaluate the hypothetical effects of pharmacological modulation of dopaminergic neurotransmission on the differentiation of immature neurons of the adult PCX, we studied dopamine D2 receptor (D2r) expression in this region and the relationship between dopaminergic fibers and immature neurons (defined by PSA-NCAM expression). In addition, we analyzed the density of immature neurons after chronic treatments with an antagonist and an agonist of D2r: haloperidol and PPHT, respectively. Many dopaminergic fibers were observed in close apposition to PSA-NCAM-expressing neurons, which also coexpressed D2r. Chronic treatment with haloperidol significantly increased the number of PSA-NCAM immunoreactive cells, while PPHT treatment decreased it. These results indicate a prominent role of dopamine, through D2r and PSA-NCAM, on the regulation of the final steps of development of immature neurons in the adult PCX.

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Dopamine D2 receptor blocking effect of imipramine in the rat hippocampus

Cited by 7 publications

References 18 publications

Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans

Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans

Classification of Psychotropic Drugs Based on Pharmaco-electrocorticographic Studies in Vigilance-Controlled Rats

Effects of Dopamine on the Immature Neurons of the Adult Rat Piriform Cortex

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