scholarly journals Nucleus Accumbens Chemogenetic Inhibition Suppresses Amphetamine-Induced Ultrasonic Vocalizations in Male and Female Rats

2021 ◽  
Vol 11 (10) ◽  
pp. 1255
Author(s):  
Kate A. Lawson ◽  
Abigail Y. Flores ◽  
Rachael E. Hokenson ◽  
Christina M. Ruiz ◽  
Stephen V. Mahler

Adult rats emit ultrasonic vocalizations (USVs) related to their affective states, potentially providing information about their subjective experiences during behavioral neuroscience experiments. If so, USVs might provide an important link between invasive animal preclinical studies and human studies in which subjective states can be readily queried. Here, we induced USVs in male and female Long Evans rats using acute amphetamine (2 mg/kg), and asked how reversibly inhibiting nucleus accumbens neurons using designer receptors exclusively activated by designer drugs (DREADDs) impacts USV production. We analyzed USV characteristics using “Deepsqueak” software, and manually categorized detected calls into four previously defined subtypes. We found that systemic administration of the DREADD agonist clozapine-n-oxide, relative to vehicle in the same rats, suppressed the number of frequency-modulated and trill-containing USVs without impacting high frequency, unmodulated (flat) USVs, nor the small number of low-frequency USVs observed. Using chemogenetics, these results thus confirm that nucleus accumbens neurons are essential for production of amphetamine-induced frequency-modulated USVs. They also support the premise of further investigating the characteristics and subcategories of these calls as a window into the subjective effects of neural manipulations, with potential future clinical applications.

2020 ◽  
Author(s):  
Michael A Taffe ◽  
Jacques D Nguyen ◽  
Sophia A Vandewater ◽  
Yanabel Grant ◽  
Tobin J Dickerson

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, "flakka") reported in the popular press. As with other designer drugs, diversification of cathiones has been driven by desireable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Male and female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion and body temperature were assessed in female rats. The α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity in female and male rats, whereas α-PPP was only effective in female rats. Inhalation of α-PHP or α-PVP by female rats suppressed wheel activity for an abbreviated duration, compared with the injection route. Spontaneous activity was increased in a dose-dependent manner by all three compounds in female rats, and a small decrements in body temperature were observed after the highest dose of all three compounds. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in both male and female rats. Differences were minor and were mostly in potency and the duration of activity. Abuse liability is therefore likely to be equivalent for all three pyrrolidino-phenones.


1973 ◽  
Vol 74 (1) ◽  
pp. 88-104 ◽  
Author(s):  
T. Jolín ◽  
M. J. Tarin ◽  
M. D. Garcia

ABSTRACT Male and female rats of varying ages were placad on a low iodine diet (LID) plus KClO4 or 6-propyl-2-thiouracil (PTU) or on the same diet supplemented with I (control rats). Goitrogenesis was also induced with LID plus PTU in gonadectomized animals of both sexes. The weight of the control and goitrogen treated animals, and the weight and iodine content of their thyroids were determined, as well as the plasma PBI, TSH, insulin and glucose levels. The pituitary GH-like protein content was assessed by disc electrophoresis on polyacrylamide gels. If goitrogenesis was induced in young rats of both sexes starting with rats of the same age, body weight (B.W.) and pituitary growth hormone (GH) content, it was found that both the males and females developed goitres of the same size. On the contrary, when goitrogenesis was induced in adult animals, it was found that male rats, that had larger B.W. and pituitary GH content than age-paired females, developed larger goitres. However, both male and female rats were in a hypothyroid condition of comparable degree as judged by the thyroidal iodine content and the plasma PBI and TSH levels. When all the data on the PTU or KClO4-treated male and female rats of varying age and B.W. were considered together, it was observed that the weights of the thyroids increased proportionally to B.W. However, a difference in the slope of the regression of the thyroid weight over B.W. was found between male and female rats, due to the fact that adult male rats develop larger goitres than female animals. In addition, in the male rats treated with PTU, gonadectomy decreased the B.W., pituitary content of GH-like protein and, concomitantly, the size of the goitre decreased; an opposite effect was induced by ovariectomy on the female animals. However, when goitrogenesis was induced in weight-paired adult rats of both sexes, the male animals still developed larger goitres than the females. Among all the parameters studied here, the only ones which appeared to bear a consistent relationship with the size of the goitres in rats of different sexes, treated with a given goitrogen, were the rate of body growth and the amount of a pituitary GH-like protein found before the onset of the goitrogen treatment. Moreover, though the pituitary content of the GH-like protein decreased as a consequence of goitrogen treatment, it was still somewhat higher in male that in female animals. The present results suggest that GH may somehow be involved in the mechanism by which male and female rats on goitrogens develop goitres of different sizes, despite equally high plasma TSH levels.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.


2001 ◽  
Vol 22 (5) ◽  
pp. 340-344 ◽  
Author(s):  
Moh'd-Ali Al-Akhras ◽  
Ahmed Elbetieha ◽  
Mohammed-Khair Hasan ◽  
Imaddin Al-Omari ◽  
Homa Darmani ◽  
...  

1996 ◽  
Vol 134 (5) ◽  
pp. 626-632 ◽  
Author(s):  
S Lumbroso ◽  
F Sandillon ◽  
V Georget ◽  
JM Lobaccaro ◽  
AO Brinkmann ◽  
...  

Lumbroso S. Sandillon F, Georget V. Lobaccaro JM, Brinkmann AO, Privat A, Sultan C. Immunohistochemical localization and immunoblotting of androgen receptor in spinal neurons of male and female rats. Eur J Endocrinol 1996:134;626–32. ISSN 0804–4643 Androgen activity in the central nervous system, as in other tissues, is mediated by the androgen receptor. We performed the precise localization of the androgen receptor in spinal cord of male and female adult rats by immunohistochemistry using polyclonal antibodies. Light microscopy indicated immunoreactivity in the anterior horn with a strong staining in motoneurons, but staining was also observed in the posterior horn. Electron microscopy showed a predominant nuclear immunostaining. A weaker but significant immunoreactive androgen receptor was also noted in the perinuclear/ intracysternal position. Moreover, no differences were found between male and female rats. Immuno-blotting demonstrated that the androgen receptor is expressed in both ventral and dorsal spinal cord, with an apparent molecular mass identical to that noted in other androgen-dependent tissues. The expression of androgen receptor in motoneurons corroborates the role of androgens in motoneuron growth, development and regeneration and underlies the possibility that androgen receptor abnormality leads to the motoneuron degeneration observed in X-linked spinal and bulbar muscular atrophy. Charles Sultan, Unité BEDR, Hôpital Lapeyronie, 34295 Montpellier, France


2005 ◽  
Vol 79 (2) ◽  
pp. 105-111 ◽  
Author(s):  
M.A. Abu-Madi ◽  
J.M. Behnke ◽  
M. Mikhail ◽  
J.W. Lewis ◽  
M.L. Al-Kaabi

AbstractA total of 179 urban rats were sampled in the city of Doha in Qatar across the winter seasons (February–April) of 2002 and 2003. Only two parasites were identified, with overall prevalences of 35.8% and 41.3% for the cestodeHymenolepis diminutaand the fleaXenopsylla astiarespectively. The prevalence ofH. diminutawas markedly influenced by both year of study and host age, being higher in 2003 and amongst older rats. The abundance of infection ofH. diminutawas influenced by the year of study, host age and sex. Worm burdens in adult rats were almost twice as heavy in males compared with females and adults of both sexes harboured heavier infections than juveniles. The prevalence ofX. astiawas influenced by both year and host age, being higher in juvenile rats in 2002 and in adults in 2003. The abundance ofX. astiawas significantly higher in 2003 and both male and female rats showed similar abundances, but in 2003 females were more heavily infested. Reasons for this are discussed in relation to the differing foraging strategies shown by male and female rats. The prevalence and abundance profiles for bothH. diminutaandX. astiawere higher overall in 2003 due to a significant increase in the rat population density, although this did not reflect in any increase in parasite species richness. Rats that were infected withH. diminutawere almost twice as likely to be infected withX. astiathan those without the cestode, but when controlled for the effects of year, host age and sex, no quantitative interactions were detected between the two parasite species.


2013 ◽  
pp. S99-S108 ◽  
Author(s):  
R. ŠLAMBEROVÁ ◽  
E. MACÚCHOVÁ ◽  
K. NOHEJLOVÁ-DEYKUN ◽  
B. SCHUTOVÁ ◽  
L. HRUBÁ ◽  
...  

The aim of the present study was to compare the response to acute application of several drugs in adult male and female rats prenatally exposed to methamphetamine (MA). Spontaneous locomotor activity and exploratory behavior of adult male and female rats prenatally exposed to MA (5 mg/kg) or saline were tested in a Laboras apparatus (Metris B.V., Netherlands) for 1 h. Challenge dose of the examined drug [amphetamine – 5 mg/kg; cocaine – 5mg/kg; MDMA (3,4-methylenedioxymethamphetamine) – 5 mg/kg; morphine – 5 mg/kg; THC (delta9-tetrahydrocannabinol) – 2 mg/kg] or saline was injected prior to testing. Our data demonstrate that prenatal MA exposure did not affect behavior in male rats with cocaine or morphine treatment, but increased locomotion and exploration in females. Application of amphetamine and MDMA in adulthood increased activity in both sexes, while cocaine and THC only in female rats. Morphine, on the other hand, decreased the activity in the Laboras test in both sexes. As far as sex and estrous cycle is concerned, the present study shows that males were generally less active than females and also females in proestrus-estrus phase of the estrous cycle were more active than females in diestrus. In conclusion, the present study shows that the prenatal MA exposure does not induce general sensitization but affects the sensitivity to drugs dependently to mechanism of drug action and with respect to gonadal hormones.


2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.


Author(s):  
Pınar Karakaş ◽  
Memduha Gülhal Bozkır ◽  
Fahri Dere ◽  
Enver Melik ◽  
Emine Babar Melik ◽  
...  

Objectives:To examine the ultrastructural effects of maternal deprivation during developmental periods of limbi-chypothalamo-pituitary-adrenal system on hippocampal dendritic structures in adult rats.Methods:The experiments were carried out with male and female wistar rats in our department. The rats were mated and, after birth, the pups were divided into four groups. The first group (control group) pups remained undisturbed with their dam until postweaning day 22. Maternal deprived groups were separated from their dams for 24 hours at postnatal day 4, 9 and 18. The subjects were provided with food and water ad libitum until 3-months-of-age. At the third month, the rats were transcardially perfused, samples were taken from CA1 and CA3 regions of the hippocampus. Tissues were prepared for electron microscopy.Results:When the data were analyzed, there were no differences between male and female rats in both ultrastructure and semiquantitative analysis of axodendritic synapses. The ultrastructure of Group 1 was seen as normal while in the second Group some neurons nuclear envelope made deep invagination into the nucleus. Additionally, axodendritic synapses were found normal. In Group 3, micrographs and axodendritic synapses were showed normal structure. However, in Group 4 in some neurons invaginations were seen similar to Group 2. Axodendritic synapses were found to be normal.Conclusion:These experiments establish that MD in rats produces slight ultrastructural changes and decreases the number of synapses in CA1 and CA3 subregions of the hippocampus.


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