-
Journal of Dairy Science Jun 2006The role of dopamine in regulating glucocorticoid and prolactin secretion was investigated in lactating Holstein cows by characterizing serum cortisol and prolactin...
The role of dopamine in regulating glucocorticoid and prolactin secretion was investigated in lactating Holstein cows by characterizing serum cortisol and prolactin responses to fluphenazine, a dopamine receptor antagonist. Twelve anovulatory cows received an intravenous bolus injection of either saline (n = 6) or 0.3 mg of fluphenazine/kg of body weight (n = 6) in wk 2 postpartum. Blood samples were collected every 30 min for 4 h before and 4 h after saline or fluphenazine injection. Serum progesterone concentration was 0.13 +/- 0.1 ng/mL and did not differ between groups. No difference in serum cortisol concentrations was detected between groups before treatments. Fluphenazine increased serum cortisol concentrations within 30 min after fluphenazine administration (>30 ng/mL) and concentrations remained elevated throughout the sampling period. Cortisol remained unchanged in saline-treated cows (<10 ng/mL). Prolactin concentrations also increased after fluphenazine administration (103.1 +/- 3.1 ng/mL), but were unaffected by saline (18 +/- 3.1 ng/mL). Prolactin concentrations remained elevated throughout the sampling period in fluphenazine-treated cows. Our results indicated that a dopamine antagonist increased cortisol, suggesting that endogenous dopamine, at least in part, regulates cortisol and prolactin secretion. These effects are regulated through dopamine receptors in anovulatory lactating dairy cows during the early postpartum period.
Topics: Animals; Cattle; Dopamine; Dopamine Antagonists; Female; Fluphenazine; Hydrocortisone; Lactation; Prolactin
PubMed: 16702268
DOI: 10.3168/jds.S0022-0302(06)72272-X -
Psychopharmacology Apr 2016Dopamine (DA) plays a key role in reward-seeking behaviours. Accumulating evidence from animal and human studies suggests that human sexual reward learning may also... (Randomized Controlled Trial)
Randomized Controlled Trial
RATIONALE
Dopamine (DA) plays a key role in reward-seeking behaviours. Accumulating evidence from animal and human studies suggests that human sexual reward learning may also depend on DA transmission. However, research on the role of DA in human sexual reward learning is completely lacking.
OBJECTIVES
To investigate whether DA antagonism attenuates classical conditioning of sexual response in humans.
METHODS
Healthy women were randomly allocated to one of two treatment conditions: haloperidol (n = 29) or placebo (n = 29). A differential conditioning paradigm was applied with genital vibrostimulation as unconditional stimulus (US) and neutral pictures as conditional stimuli (CSs). Genital arousal was assessed, and ratings of affective value and subjective sexual arousal were obtained.
RESULTS
Haloperidol administration affected unconditional genital responding. However, no significant effects of medication were found for conditioned responding.
CONCLUSIONS
No firm conclusions can be drawn about whether female sexual reward learning implicates DA transmission since the results do not lend themselves to unambiguous interpretation.
Topics: Adolescent; Adult; Conditioning, Classical; Dopamine Antagonists; Emotions; Female; Haloperidol; Humans; Libido; Middle Aged; Reward; Sexual Behavior; Young Adult
PubMed: 26832339
DOI: 10.1007/s00213-015-4201-x -
Expert Opinion on Pharmacotherapy Apr 2017Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression... (Review)
Review
Drug development and repurposing are urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. Areas covered: We review dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence in ASD. Emerging promise of amitriptyline in ASD is discussed, together with promising BDNF effects of loxapine and amitriptyline. Expert opinion: In ASD, pharmacotherapy and specifically dopamine antagonist drugs are often prescribed for challenging behaviors including aggression. The novel antipsychotics risperidone and aripiprazole have received most study in ASD and are FDA-approved for irritability in children with ASD over age 5 years; individuals with ASD are prone to weight gain, Type II diabetes and associated side effects. Low dose loxapine has properties of classical and novel antipsychotics but importantly appears more weight neutral, and with promising use in adolescents and adults with ASD. Amitriptyline appears effective in ASD for irritability, aggression, gastrointestinal problems, and insomnia, in children, adolescents and adults however our adult data on amitriptyline in ASD is still in preparation for publication. Both loxapine and amitriptyline may stimulate BDNF; further studies are warranted.
Topics: Adolescent; Adult; Amitriptyline; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Brain-Derived Neurotrophic Factor; Child; Dopamine Antagonists; Humans; Irritable Mood; Loxapine; Risperidone
PubMed: 28335658
DOI: 10.1080/14656566.2017.1308483 -
CNS Neuroscience & Therapeutics 2008Eticlopride is a substituted benzamide analog with high affinity and selectivity for dopamine (DA) D2-like receptors that was initially developed as a potential... (Review)
Review
Eticlopride is a substituted benzamide analog with high affinity and selectivity for dopamine (DA) D2-like receptors that was initially developed as a potential antipsychotic agent. A great deal of research has utilized this drug to better understand central DA receptor function, the role of D2-like receptors in behavior, and the influence of blockade of these receptors on several preclinical animal models. This review highlights research utilizing this drug and compares it to typical and atypical antipsychotics used clinically. First, we describe structure-activity relationships as it relates to binding at DA receptors and the consequences on behavior. This is followed by a discussion of several imaging strategies including the use of eticlopride for in vivo, in vitro, and ex vivo examination of DA D2-like receptor densities and function. Finally, we discuss the use of eticlopride in several behavioral models predictive of antipsychotic activity, extrapyramidal side effects (EPS), and learning and memory. While eticlopride is not used clinically, it remains a viable research tool for understanding DA receptor function and behavior.
Topics: Animals; Antipsychotic Agents; Behavior, Animal; Dopamine; Dopamine Antagonists; Humans; Salicylamides; Signal Transduction
PubMed: 18801115
DOI: 10.1111/j.1755-5949.2008.00047.x -
Learning & Memory (Cold Spring Harbor,... Jun 2022Dopamine participates in encoding memories and could either encode rewarding/aversive value of unconditioned stimuli or act as a novelty signal triggering contextual...
Dopamine participates in encoding memories and could either encode rewarding/aversive value of unconditioned stimuli or act as a novelty signal triggering contextual learning. Here we show that intraperitoneal injection of the dopamine D1/5R antagonist SCH23390 impairs contextual fear conditioning and tone-shock association, while intrahippocampal injection only impairs contextual fear conditioning. By using the context pre-exposure facilitation effect test, we show that SCH23390 is able to block the encoding of the context during the pre-exposure phase. Thus, we provide additional evidence that dopamine is involved in encoding conjunctive representations of new contexts.
Topics: Conditioning, Classical; Dopamine; Dopamine Antagonists; Fear; Learning; Receptors, Dopamine D1
PubMed: 35577394
DOI: 10.1101/lm.053555.121 -
Reproduction in Domestic Animals =... Mar 2023This study aimed to test the hypothesis that sulpiride can increase the concentration of circulating gonadotropin that can promote puberty in pre-pubertal ewe lambs....
This study aimed to test the hypothesis that sulpiride can increase the concentration of circulating gonadotropin that can promote puberty in pre-pubertal ewe lambs. Here, 12 1-3-year-old Merino rams and 60 7-9-month-old Merino sheep were included in the study. The sheep were randomly divided into sulpiride (n = 30) and control (n = 30) groups. The sulpiride group was subcutaneously injected with 0.6 mg/kg sulpiride twice daily (morning and evening) for 9 days. During these 9 days, blood samples were taken from the sheep before drug administration and at 4 h after every drug administration. The number of ovulating animals in the sulpiride group was significantly higher than that in the control group (90% vs. 32%). No oestrous signs were observed in either group during ram release. Further, there were no differences in the levels of mean follicle-stimulating hormone in the two groups based on treatment (p = .2), time (p = .3) or treatment-by-time interaction (p = .3). After sulpiride administration, the luteinizing hormone (LH) levels of the sulpiride group rapidly increased and remained stable for a long time, whereas physiological LH fluctuations in the control group remained unchanged. Within-group changes in terms of LH concentrations were significant for both groups (p < .001), whereas LH pulse frequency was significantly different between the sulpiride group (p = .03). Therefore, it is concluded that sulpiride can be used as a non-steroidal alternative to stimulate pre-pubertal ewe lambs and sheep during anoestrus.
Topics: Female; Animals; Sheep; Sulpiride; Dopamine Antagonists; Sexual Maturation; Follicle Stimulating Hormone; Ovulation
PubMed: 36369678
DOI: 10.1111/rda.14295 -
Naunyn-Schmiedeberg's Archives of... Feb 2013The potential of D(3) receptor antagonism to treat positive, negative, and cognitive symptoms of schizophrenia is reviewed on the basis of preclinical results and... (Review)
Review
The potential of D(3) receptor antagonism to treat positive, negative, and cognitive symptoms of schizophrenia is reviewed on the basis of preclinical results and preliminary clinical data. Dopamine D(3) receptors are expressed in mesencephalic, limbic, and cortical areas relevant to psychotic and cognitive symptoms of schizophrenia. As expected, selective dopamine D(3) receptor antagonists are not effective in antipsychotic animal models, reflecting D(2) receptor antagonism. However, selective D(3) receptor antagonists affect electrical activity of dopamine neurons in the ventral tegmental area similar to atypical antipsychotics, counteract effects produced by NMDA glutamate receptor blockade, and enhance cortical dopamine and acetylcholine in microdialysis. In contrast to dopamine D(2) receptor antagonists, D(3) antagonists positively influence a variety of social and cognitive behaviors in rodents, including tests representing cognitive flexibility and executive function, which are both impaired in schizophrenia patients. Despite considerable affinity for D(3) receptors, the second-generation antipsychotics clozapine, risperidone, and olanzapine when administered to patients with schizophrenia seem not to occupy D(3) receptors sufficiently to derive any conclusion on a D(3)-mediated therapeutic benefit. ABT-925, the first selective D(3) receptor antagonist, was recently studied in patients with schizophrenia. It produced cognitive signals but did not achieve sufficient D(3) receptor occupancy to test the hypothesis that D(3) receptor antagonism is of therapeutic value to treat symptoms of schizophrenia. Based on mechanistic and experimental considerations and due to the fact that D(3) receptor antagonism can inhibit extrapyramidal symptoms and produce neither anhedonia nor metabolic adverse effects, the development and clinical testing of newer D(3) receptor antagonists with high potency at D(3) receptors, enabling sufficient receptor occupancy, is highly warranted.
Topics: Animals; Antipsychotic Agents; Brain; Cognition; Dopamine Antagonists; Humans; Receptors, Dopamine D3; Schizophrenia
PubMed: 23128852
DOI: 10.1007/s00210-012-0806-3 -
Birth Defects Research Oct 2018An extended-release molindone (a dopamine D and serotonin antagonist) is currently being developed as a novel treatment for impulsive aggression (IA) in patients...
BACKGROUND
An extended-release molindone (a dopamine D and serotonin antagonist) is currently being developed as a novel treatment for impulsive aggression (IA) in patients optimally treated for ADHD. Oral Good Laboratory Practice reproductive toxicology studies (fertility and early embryonic [FEE], prenatal/postnatal [PPN], embryo-fetal development [EFD]) were conducted with molindone HCl using International Conference on Harmonisation (ICH) S5(R2)-compliant protocols.
METHODS
In the FEE study, 0, 5, 15, or 30 mg kg day was administered to female (2 weeks premating through implantation) and male (4 weeks premating for 57 days) rats, and fertility parameters were evaluated. In the EFD studies, rats received 0, 5, 20, or 40 mg kg day on gestational days (GDs) 6-17; rabbits received 0, 5, 10, or 15 mg kg day on GDs 6-18. Ovarian/uterine and fetal parameters were evaluated at term. In the PPN study, F rats received 0, 5, 20, or 40 mg kg day (GD6-LD21); behavior and reproduction were evaluated in F offspring.
RESULTS
Parental hypoactivity and reduced body weight gain occurred in all studies. In the FEE, prolonged estrous cycles and delayed mating occurred at ≥15 mg kg day , without effects on fertility or embryonic development. No developmental toxicity occurred in F fetuses. In F pups, reduced preweaning growth was observed at 40 mg kg day , but there were no effects on postweaning growth, behavior, or reproduction.
CONCLUSIONS
Molindone was not developmentally toxic in rats or rabbits at 69X and 6X clinical exposures, confirming the reproductive safety of molindone. Changes in estrous cyclicity were related to species-specific pharmacological effects of molindone in rodents and are not considered relevant to human risk.
Topics: Animals; Body Weight; Dopamine Antagonists; Embryonic Development; Female; Fertility; Male; Molindone; Pregnancy; Prenatal Exposure Delayed Effects; Rabbits; Rats; Rats, Wistar; Reproduction
PubMed: 30230712
DOI: 10.1002/bdr2.1381 -
Journal of Neurophysiology Jul 2022Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is...
Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is presumed that drugs do not directly affect ASSRs because its abnormalities are associated with schizophrenia. Therefore, to investigate the direct effect of drugs on ASSRs, we established an ASSR evaluation system for common marmosets in a naïve state. Dopamine D1 receptor stimulation (SKF-81297, 2 mg/kg ip) significantly increased evoked power (EP) at 40 Hz. The phase locking factor (PLF) was increased significantly at 20, 30, 40, and 80 Hz. However, administration of a dopamine D1 receptor antagonist (SCH-39166, 0.3 mg/kg ip) resulted in a significant decrease in EP and PLF at 30 Hz. Dopamine D2 receptor stimulation (quinpirole, 1 mg/kg im) tended to increase EP and induced power (IP) at all frequencies, and a significant difference was observed at 30 Hz IP. There was no change in PLF at all frequencies. In addition, dopamine D2 receptor blockade (raclopride, 3 mg/kg ip) reduced EP and PLF at 30 Hz. Subcutaneous administration of the serotonin dopamine antagonist, risperidone (0.3 mg/kg), tended to increase IP and decrease PLF, but not significantly. Taken together, it is possible to compare the differences in the mode of action of drugs on ASSRs using naïve nonhuman primates. We measured the effects of dopamine receptor-related compounds on ASSR in marmosets. D1 receptor stimulation increased the phase locking factor (PLF) and evoked power (EP), and reduced the induced power (IP). D2 receptor stimulation increased the IP. D1 and D2 receptor blockers reduced the PLF and EP at 30 Hz. Different modes of action of various drugs related to psychiatric disorders were evaluated by administering antipsychotic drugs to naïve marmosets.
Topics: Acoustic Stimulation; Animals; Antipsychotic Agents; Callithrix; Dopamine Antagonists; Evoked Potentials, Auditory; Humans; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35583977
DOI: 10.1152/jn.00147.2022 -
Psychopharmacology Mar 1995The FAST and SLOW lines of mice are being selectively bred in replicate for differential sensitivities to the locomotor activating effects of ethanol. Whereas FAST-1 and...
The FAST and SLOW lines of mice are being selectively bred in replicate for differential sensitivities to the locomotor activating effects of ethanol. Whereas FAST-1 and FAST-2 mice are stimulated by 2.0 g/kg ethanol, SLOW-1 and SLOW-2 mice are not stimulated, and are often depressed, by this dose. The dopamine antagonists, SCH-23390 (D1) and raclopride (D2), produced dose-dependent decreases in the locomotor activity of EtOH-naive mice of both lines and replicates; however, FAST and SLOW mice were not differentially sensitive to these effects. The absence of a line difference in activity response to the dopamine antagonists suggests that dopamine receptor function has not been altered by selective breeding for differences in sensitivity to the stimulant effects of ethanol. The ethanol-stimulated activity of FAST-1 and FAST-2 mice was decreased by administration of the dopamine antagonists, haloperidol and raclopride, at doses that had no effect on basal locomotor activity. SCH-23390 decreased ethanol-stimulated activity of FAST-1, but not FAST-2 mice. The ethanol-induced activity changes of SLOW mice were generally unaffected by antagonist administration. These results suggest a role for dopaminergic systems in mediating ethanol-stimulated activity in selectively bred FAST mice. Coadministration of SCH-23390 and raclopride decreased ethanol-induced activation to a greater degree than either drug alone, further suggesting that both D1 and D2 receptor systems contribute to the full expression of the ethanol stimulant response.
Topics: Animals; Benzazepines; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Ethanol; Haloperidol; Mice; Motor Activity; Raclopride; Receptors, Dopamine D1; Salicylamides
PubMed: 7597119
DOI: 10.1007/BF02245246