Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid ...

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors

It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.

Prolactin induces adrenal hypertrophy

Although adrenocorticotropic hormone is generally considered to play a major role in the regulation of adrenal glucocorticoid secretion, several reports have suggested that other pituitary hormones (e.g., prolactin) also play a significant role in the regulation of adrenal function. The aim of the present study was to measure the adrenocortical cell area and to determine the effects of the transition from the prepubertal to the postpubertal period on the hyperprolactinemic state induced by domperidone (4.0 mg kg-1 day-1, sc). In hyperprolactinemic adult and young rats, the adrenals were heavier, as determined at necropsy, than in the respective controls: adults (30 days: 0.16 ± 0.008 and 0.11 ± 0.007; 46 days: 0.17 ± 0.006 and 0.12 ± 0.008, and 61 days: 0.17 ± 0.008 and 0.10 ± 0.004 mg for treated and control animals, respectively; P < 0.05), and young rats (30 days: 0.19 ± 0.003 and 0.16 ± 0.007, and 60 days: 0.16 ± 0.006 and 0.13 ± 0.009 mg; P < 0.05). We selected randomly a circular area in which we counted the nuclei of adrenocortical cells. The area of zona fasciculata cells was increased in hyperprolactinemic adult and young rats compared to controls: adults: (61 days: 524.90 ± 47.85 and 244.84 ± 9.03 æm² for treated and control animals, respectively; P < 0.05), and young rats: (15 days: 462.30 ± 16.24 and 414.28 ± 18.19; 60 days: 640.51 ± 12.91 and 480.24 ± 22.79 æm²; P < 0.05). Based on these data we conclude that the increase in adrenal weight observed in the hyperprolactinemic animals may be due to prolactin-induced adrenocortical cell hypertrophy.

Reproductive experience influences grooming behavior during pregnancy in rats

The pregnancy-induced increase in self-licking observed in rats is important for mammary gland development and lactation. Reproductive experience has epidemiologial implications such as a decrease in the incidence of mammary gland cancer in women and it also influences various behavioral, neurochemical and endocrine parameters. The aim of the present study was to investigate the influence of reproductive experience on grooming behavior patterns during pregnancy in rats. Self-grooming behavior was measured in age-matched virgin, primi- and multigravid (days 7, 8, 9, 19, and 20 of pregnancy) rats. General grooming (head, forelimbs and shoulders) was not significantly different among virgin, primi- and multigravid rats during pregnancy. Confirming previous work, pregnant rats spent significantly more time in specific grooming (mammary glands, nipple lines, genital and pelvic regions) than did virgin animals. In addition, self- licking of mammary glands was significantly increased in multi- as compared to primigravid rats on days 8, 9, 19 and 20 of pregnancy. The increase in mammary gland grooming observed in multigravid rats appears to be a consequence of previous reproductive experience. These data show that reproductive experience modulates mammary gland grooming during pregnancy, possibly contributing to successful reproduction

Dopaminergic modulation of grooming behavior in virgin and pregnant rats

Dopamine receptors are involved in the expression of grooming behavior. The pregnancy-induced increase in self-licking observed in rats is important for mammary gland development and lactation. This study focuses on the role of dopamine receptor subtypes in grooming behavior of virgin and pregnant female rats. General and mammary gland grooming were measured in virgin rats treated with 0.25 mg/kg of the D1-like agonist SKF-81297 and antagonist SKF-83566 and the D2-like agonist lisuride and antagonist sulpiride. The effects of 0.01 and 0.25 mg/kg doses of the same agonists and antagonists were evaluated in pregnant rats as well. In virgin animals both SKF-83566 and sulpiride treatments significantly reduced the time spent in general grooming, while none of the dopamine agonists was able to significantly change any parameter of general grooming. Time spent in grooming directed at the mammary glands was not affected significantly by any of the drug treatments in virgin rats. All drugs tested significantly decreased the frequency of and the time spent with general grooming, while SKF-81297 treatment alone did not significantly reduce the duration of mammary gland grooming in pregnant rats. These data show that in female rats the behavioral effects of D1-like and D2-like dopamine receptor stimulation and blockade differ according to physiological state. The results suggest that dopamine receptors may play specific roles modulating grooming behavior in pregnant rats. Since grooming of the mammary gland during pregnancy may influence lactation, this aspect is relevant for studies regarding the perinatal use of dopamine-related drugs

The brain decade in debate: VIII. Peptide hormones and behavior: cholecystokinin and prolactin

This article is a transcription of an electronic symposium held on November 28, 2000 in which active researchers were invited by the Brazilian Society of Neuroscience and Behavior (SBNeC) to discuss the advances of the last decade in the peptide field with particular focus on central actions of prolactin and cholecystokinin. The comments in this symposium reflect the diversity of prolactin and cholecystokinin research and demonstrate how the field has matured. Since both peptides play a role in reproductive behaviors, particularly mother-infant interactions, this was the starting point of the discussion. Recent findings on the role of the receptor subtypes as well as interaction with other peptides in this context were also discussed. Another issue discussed was the possible role of these peptides in dopamine-mediated rewarding systems. Both prolactin and cholecystokinin are involved in mechanisms controlling food intake and somatic pain thresholds. The role of peripheral inputs through vagal afferents modulating behavior was stressed. The advent of knockout animals as potential generators of new knowledge in this field was also addressed. Finally, interactions with other neuropeptides and investigation of the role of these peptides in other fields such as immunology were mentioned. Knowledge about the central functions of prolactin and cholecystokinin has shown important advances. The role of these peptides in neurological and psychiatric syndromes such as anorexia, drug abuse and physiological disturbances that lead to a compromised maternal behavior seems relevant

Influence of lactation on motor activity and elevated plus maze behavior

Lactating rats show less noise-induced freezing and fewer inhibitory responses on the 6th day post-delivery when submitted to water and food deprivation in a classical conflict paradigm. Lactating mice go more often to the illuminated chamber in a light-dark cage and stay longer in it than virgin females. The present study was designed to assess the influence of this physiological state, i.e. lactation, on the elevated plus maze (EPM) and open-field behavior in adult female rats. Total (TL) and central (CL) locomotion and rearing (RF) frequencies were measured in an open-field. Number of entries into the open and closed arms as well as the time spent in each of these arms were measured in the EPM. Percent time spent and number of entries into the open arms were calculated and compared. In the open-field, TL was significantly decreased (115 + 10.6 vs 150 + 11.6) while CL and RF did not differ from those presented by virgin rats. In the EPM, lactating rats displayed a significant reduction in percent time spent (10.9 ñ 1.5 vs 17.4 ñ 2.3) in the open arms as well as a tendency to a reduction in percent entries into the open arms (35.7 ñ 4.7 vs 45.7 ñ 4.3). These results show that the physiological state of lactation modulates the open-field and EPM behaviors in rats.

Is perinatal picrotoxin anxiogenic?

Female Wistar rats were exposed to a subconvulsant dose of picrotoxin (0.75 mg/Kg,sc) on day 18 of pregnancy, immediately after paturition and daily during the first 5 days of lactation. In adulthood, the offspring were tested in an open-field, in an elevated plus maze and for social interaction. Results showed increased locomotor activity (75 days of age) and decreased social interaction (90 days of age) in experimental male rats compared to control male rats. No effects on behaviors related to anxiety were observed in males or females tested in the plus maze apparatus. An additional comparison of the activity male animals perinatally treated with picrotoxin showed a lack of the classical sexual dimorphic responses in the open-field (control male = 68.7 ñ 6.31; control female = 98.4 ñ 6.31; edxperimental male = 89.6 ñ 6.32; experimental female = 113.2 ñ 4.74). We suggest that perinatal picrotoxin exposure may interfere with normal male masculinization rather increasing anxiety in male rats

Intracerebroventricular administration of cholecystokinin reduces stereotypy in dopamine supersensitive rats

Cholecystokinin (CCK-8) coexists with dopamine in some neurons and modulates dopaminergic neurotransmission. In the present study we determined the effect of CCK-8 on stereotyped behavior in supersensitive dopaminergic system. Adult male Wistar rats, weighing 200-250 g, were used. Dopaminergic supersensitivity was induced by long-term haloperidol (HAL) treatment (30 days: 1.0 mg/kg twice a day). Seventy-two hours after HAL withdrawal animals received CCK-8 (14.5 nmol/5 µl) or saline intracerebroventricularly (icv) before being tested for apomorphine (APO, 0.6 mg/kg, sc)-induced stereotyped behavior. experimental groups were: long-term HAL-treated rats that received saline (HSAL, N = 9) or CCK-8 (HCCK, N = 11) icvand long-term saline-treated rats that received CCK-8(SCCK,N = 9) or saline (SSAL, N = 8) icv. As expected, HSAL rats showed statistically significant higher stereotypy scores than SSAL rats (42 + or - 1.7 vs 31 + or - 1.6; P<0.05) and CCK-8 icv reduces stereotypy in dopaminergic-supersensitive rats, and suggest that the dopamine supersensitivity phenomenon can be modulated by CCK-8

Developmental expression of sexual differences in open-field behaviour and plasma cholinesterase activity in male, female and masculinized female rats

Sabe-se que algumas diferenças sexuais no metabolismo e no comportamento estäo relacionadas com o efeito neonatal da testosterona e outras näo sofrem esse tipo de influência. O objetivo desses experimentos foi estudar o desenvolvimento das diferenças sexuais na atividade da colinesterase plasmática e de determinar se essas diferenças seriam relacionadas com a exposiçäo pós-natal à testosterona em ratos. A atividade geral no campo aberto foi também verificada como um indicador comportamental das açöes da testosterona na diferenciaçäo sexual do sistema nervoso central. Foram usados três grupos de animais: machos normais, fêmeas normais e fêmeas masculinizadas (1 mg testosterona, SC, no 2§ dia de vida pós-natal). A atividade geral no campo aberto foi medida durante três dias consecutivos logo após o desmame (21-23 dias de idade), durante o início da puberdade (30-36 dias de idade) e nos adultos (90-110 dias de idade); a atividade da colinesterase plasmática foi medida aos 22, 30-36 e 90-110 dias de idade. Como esperado, foi encontrada uma diferença sexual no campo aberto entre machos e fêmeas normais. O tratamento pós-natal com andrógeno nas fêmeas diminuiu a atividade no campo aberto na idade adulta a padröes similares àqueles observados para machos normais. Foram observadas diferenças similares logo após o desmame, mas näo aos 22 e aos 30-36 dias de idade. Em contraste, foram observadas diferenças significantes na atividade da colinesterase de animais adultos mas näo nos dias 22 e 30-33 dias de idade. Quando comparadas às fêmeas normais, as fêmeas masculinizadas näo apresentaram diferenças na atividade da colinesterase plasmática, sendo que esses dois grupos foram diferentes dos machos. Esses resultados sugerem que as diferenças sexuais na atividade da colinesterase plasmática de ratos adultos, näo säo dependentes de exposiçäo à testosterona durante o início da vida pós-natal. Além disso os resultados demonstram que sob esse estresse (desmame) as diferenças sexuais no comportamento no campo aberto podem ser observadas já aos 21-23 dias de idade

Effects of chronic domperidone treatment on rat conditioned avoidance behavior

The effects of chronic administration of domperidone (DOM), a peripherally acting anti-emetic and hyperprolactinemic D2-dopaminoceptor antagonisti, on active and inhibitory conditioned behavior were tested on male and female rats. DOM (4 mg/Kg) was injected ip daily either for 5 or 30 days. Although treatment for 5 days failed to effect experimental parameters, treatment for 30 days impaired the performance of active conditioned avoidance of female, but not male, rats. This effect was no longer observed 7 days after ending treatment. No effects of DOM treatment were observed on active conditioned avoidance of male rats or on inhibitory conditioned behavior of all rats. These data suggest that female rats are more susceptible to the hyperprolactinemic effects of DOM than male rats. However, an influence of estrous cycle interruption cannot be rejected

Effect of acute bromopride treatment on rat prolactin levels and sexual behavior

Acute intraperitoneal adminsitration of bromoprid (BRO), a dopamine D2 blocker used as an anti-emetic drug in gastroenterology was tested in male and female ratas for its effect on prolactin (PRL) serum levels and on sexual behavior. Rats that received 2.5 mg/Kg BRO, the lowest dose tested, showed a maximal nincrease in PRL serum levels. Male rats that received 5.0 mg/Kg BRO showed higher postejaculatory mount lactency and postejaculatory intromission latency than controls. Rats treated with 10.0 mg/Kg BRO showed higher mount latency, intromission latency, ejaculation latency, postejaculatory mount latency and a lower percentage of animals showing mount and ejaculation. Female rats that received 5.0 mg/Kg BRO showed a lower lordosis quotient. The data suggest that glockade of postynaptic dopamine D2 receptors inhibitis male and female sexual behavior and that this inhibition is not related solely to the increase in PRL lelvels

Acute bromopride treatments: effects on general activity and inhibitory avoidance in rats

Bromopride (BRO), a dopamine D2 blocker used in gastroenterology clinics, was tested acutely in rats for effects on general activity, measured in an open-field test, and on inhibitory avoidance behavior. Rats that received 2.5 and 5.0 mg/Kg BRO showed lower locomotion and rearing frequencies than controls, and 5.0 mg/Kg BRO blocked the inhibitory avoidance response. The data suggest that BRO may have neuroleptic effects