Phosphorylation of bovine prolactin eliminates luteotropic activity in the rat

Phosphorylated and nonphosphorylated prolactins were isolated from bovine pituitaries and their luteotropic activity determined in female rats. Three groups of rats in day 1 of diestrus were treated i.p. twice daily for three days with 0.25 mg of either prolactin preparation or vehicle. Rats were sacrificed each day of treatment. Serum progesterone concentrations of the groups receiving vehicle or phosphorylated prolactin were similar and the vaginal cytology of these animals indicated that phosphorylated bovine prolactin (bPRL) treatment had not prolonged diestrus. Treatment with nonphosphorylated bPRL significantly increased serum progesterone concentration and the vaginal cytology indicated a diestrus prolonged for up to 4 days. Nonphosphorylated and phosphorylated bPRLs were cleared from the blood at similar rates after i.p. injection. In vitro receptor binding studies demonstrated that phosphorylated bPRL did not bind the ovarian prolactin receptor. Nonphosphorylated, but not phosphorylated, bPRL competed with radiolabeled bovine hormone for occupancy of rat ovarian prolactin receptors. These data are the first to test the activities of phosphorylated bPRL in vivo and indicate; 1) nonphosphorylated bPRL is luteotropic, 2) phosphorylated bPRL is neither luteotropic nor a prolactin receptor agonist or antagonist and 3) phosphorylated bPRL is not dephosphorylated in vivo rapidly enough to provide sufficient biologically-active bPRL to maintain luteal function.     

Protein phosphatase activity in the rat ovary throughout pregnancy and pseudopregnancy

Specific protein phosphatase activity against protein kinase C-phosphorylated substrate was measured in the rat ovary during pseudopregnancy and pregnancy. Tissues were processed in the presence of sodium fluoride and inorganic phosphate to inhibit the phosphatase and thereby prevent autodephosphorylation of the type 2A protein phosphatase (PP2A) during homogenization. Manganese was added at the time of enzyme assay to reactivate the phosphatase. The specific activity of the protein phosphatase did not vary significantly across pseudopregnancy (p > 0.05). In contrast, the specific activity of protein phosphatase decreased significantly between Day 7 and Day 10 of pregnancy (28.8 +/- 5 pmol/min x microg protein and 20.7 +/- 2 pmol/min x microg protein, respectively; p < 0.05) and remained at the decreased value for the remainder of pregnancy. To determine whether hormones of pregnancy could regulate PP2A activity in the ovaries, pseudopregnant rats were treated with prolactin (3 IU twice a day), bromocriptine (100 microg twice a day), or estradiol benzoate (50 microg). Bromocriptine and estradiol treatments caused a decrease in PP2A-specific activity, but prolactin had no effect. Bromocriptine treatment caused a decrease in the protein content of the PP2A catalytic subunit, but prolactin and estradiol treatments had no effect. The data suggest that the specific activity and protein content of PP2A in the rat ovary are hormonally regulated.     

The discriminative stimulus effects of clomethiazole in the rat

Rats were trained in a two-lever drug discrimination procedure using saline or clomethiazole (8 mg/kg, s.c. 15 min) as the training stimuli. A criterion of 9/10 days correct lever choice was adopted to select rats for substitution tests. The clomethiazole (CMZ) cue was not especially strong, and stable performance at this level was not achieved consistently. Nevertheless, in a series of substitution tests carried out in extinction, diazepam (3 mg/kg), chlordiazepoxide (10 mg/kg), phenobarbital (60 mg/kg), dizocilpine (0.1 mg/kg) and mianserin (3.0 mg/kg) were found to substitute for the training dose of CMZ. The first two of these produced a percentage choice of the drug lever equal to that produced by the training dose of CMZ (full generalization) whereas the latter three produced only partial generalization. Ethanol, muscimol, allopregnanolone, chlorpromazine and amitriptyline did not generalize to CMZ. CMZ is known to potentiate gamma-aminobutyric acid (GABAA) receptor function, a finding supported by the generalization to CMZ of the two benzodiazepines and phenobarbital. However, not all drugs acting at GABAA receptors generalized to CMZ. Although CMZ has no affinity for the N-methyl-D-aspartate (NMDA) receptor, it antagonizes a number of pharmacological responses mediated by NMDA receptors. The generalization in the drug discrimination procedure reported here support the suggestion that altering GABA activity can modulate NMDA-mediated responses. The lack of generalization after treatment with ethanol, chlorpromazine and amitriptyline suggests that the interoceptive cues are not mediated by a generalized sedation or drug-induced motor impairment.     

Prolactin immunoreactive neurons of the rat lateral hypothalamus: immunocytochemical and ultrastructural studies

A population of neurons immunoreactive to an antiserum (AS) raised against ovine prolactin (LHPLI neurons) was previously described in the rat perifornical areas and lateral hypothalamus. In the present paper, we demonstrate by complementary immunocytochemical studies using AS to various biologically active peptides or neurotransmitters that these neurons are also detected by AS to bradykinin and to dynorphin B. Electron microscope examination shows that the LHPLI neurons are peptidergic neurons synthesizing apparently only one type of secretory granules. Numerous synapses on their perikarya and processes reflect the complexity of their relationships with other neuron populations, which have yet to be mapped and elucidated.     

Prolactin in human and rat serum and cerebrospinal fluid

Rats treated with haloperidol or bearing subcutaneous implants of prolactin-secreting tumors had elevated CSF prolactin levels compared to those observed in control rats. These levels were commensurate with the increased serum level of prolactin, although there appeared to be an upper limit to the CSF prolactin concentration. Patients with prolactin-secreting pituitary adenomas had elevated CSF hormone levels as compared to patients with non-endocrine neurologic disease. This obtained, regardless of whether the tumor was intra- or extrasellar in its growth. The implications for the route of entry of prolactin into CSF under both normal and abnormal conditions, and the potential role for CSF prolactin as part of a feedback regulatory system on pituitary prolactin release are discussed.     

Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat

The aim of this study was to investigate the efficacy of pseudoephedrine as a nasal decongestant. Patients with nasal congestion associated with common cold received two doses of medication separated by 4 hours, either 60 mg pseudoephedrine (n = 20), or placebo (n = 20). Unilateral nasal airflow was measured over a 7-hour period to record the spontaneous changes in nasal airflow associated with the nasal cycle. Minimum (F MIN) and maximum (F MAX) unilateral nasal airflows were defined as the minimum and maximum nasal airflow values for each nasal passage recorded during the 7-hour period of the study. There was no significant difference in F MAX between the two treatment groups yet there was a significant difference in F MIN (p < 0.05). No difference in total nasal airflow (TNAF) between treatment groups was found, either before or after treatment (p > 0.05). The results demonstrate that (TNAF) is not as sensitive a measure of decongestion as F MIN. The findings of this study show that pseudoephedrine had no effect on the decongestion phase of the nasal cycle, but did significantly limit the congestion phase. The decongestant action may be explained by the sympathomimetic supplementing the natural sympathetic nervous activity to the nasal blood vessels.     

Lower sphincter of the opossum esophagus in pseudopregnancy

To seek a possible role of estrogen and progesterone in the development of changes in esophageal function during pregnancy, we produced a state of pseudopregnancy by administration of hormones to a suitable animal model. Twenty-two female opossums weighing an average of 2.5 kg, were divided into two groups. The treated group received intramuscular injections of 100 microgram of estradiol valerate daily from day 1 to day 12 and 15 mg of medroxyprogesterone acetate from day 7 to day 12. The control group received no injections. Both groups underwent manometry on days 1, 7, and 12. Lower esophageal sphincter pressure decreased (P less than 0.05) in treated animals from 58 +/- 13 mm Hg and 57 +/- 11 on days 1 and 7, respectively, to 44 +/- 10 mm Hg on day 12. The lower esophageal sphincter pressure remained unchanged in control animals. In both groups, there was no change in peristaltic wave pressure, duration, or velocity in the distal 6 cm of the esophagus. No abnormal peristaltic phenomena were observed. Esophageal muscle strips prepared from treated animals showed responses to electrical field stimulation of intrinsic nerves that were like those from control animals. The same was true for responses to acetylcholine and pentagastrin. Total tissue water and total tissue potassium content did not differ in treatment and control animals.     

Social deprivation and stimulus satiation in the albino rat.

Conducted 2 experiments, with a total of 288 male Sprague-Dawley albino rats, to explore the mechanisms whereby social deprivation leads to increased sociability in rats. Exp I housed Ss alone or in pairs with additional nonsocial stimulation, with additional response opportunities, or with no added social surrogates for 3 wks prior to testing for sociability. Social deprivation led to a strong increase in sociability, and this was not ameliorated by stimulus or response enrichment. Exp II exposed alone or pair-housed Ss to handling, human contact, or no stimulation and found that human exposure did serve a social surrogate function. This result suggests that sociability in rats represents to some degree a search for complex and unpredictable stimulation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessment of the discriminative stimulus effects of cocaine in the rat: lack of interaction with opioids

The present study examined the effects of several opioid agonists and antagonists in rats trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, food-reinforced, discrimination task. Neither fentanyl, a mu agonist, nor the delta agonist BW 373U86 elicited cocaine-appropriate responding. Although pretreatment with fentanyl failed to alter the discriminative stimulus effects of low doses of cocaine, cocaine reversed the rate-suppressant effects of fentanyl. Although the kappa agonist U50,488H decreased response rates, it did not substitute for cocaine. Injection of U50,488H in combination with the training dose of cocaine (10 mg/kg) reversed the rate-suppressant effects of U50,488H but failed to affect the cocaine cue. Administration of U50,488H (3 mg/kg), in conjunction with several doses of cocaine, did not shift the cocaine dose-response curve. Naltrindole and naltrexone, delta and mu antagonists respectively, did not block the effects of cocaine. Further, naltrindole did not substitute for the cocaine cue. Complete generalization was observed to the dopamine uptake inhibitor bupropion (30 mg/kg). These results suggest that fentanyl and U50,488H, at doses that purportedly influence mesolimbic dopamine levels, do not alter the discriminative stimulus effects of cocaine. Moreover, activation of delta receptors and blockade of mu and delta receptors are similarly ineffective.     

Conditioned stimulus intensity and acquired alimentary aversions in the rat.

Studied 188 male Long-Evans hooded rats. Three groups were made ill following the ingestion of 1 of 3 intensities of salt taste and then were tested several times for aversions to each of the 3 intensities after this single training trial, yielding a 3 by 3 factorial design. ANOVA from this design revealed a significant positive effect on degree of aversion of both training intensity and testing intensity, and a significant interaction between these 2 intensity variables. The interaction was further analyzed into a component implying a multiplicative relationship between training intensity and testing intensity in determining strength of aversion, and into a component interpreted as indicating a decrement of the aversion when tested with intensities other than the training intensity. Results suggest a lawfulness of stimulus–response relationships comparable to those found in studies employing more typical conditioned responses. Previous conditioning studies, however, have demonstrated only the effect of conditioned stimulus intensity on "performance" (testing intensity effect), not on "learning" (training intensity effect). (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Startle reflex inhibition in the rat: Its persistence after extended repetition of the inhibitory stimulus.

Startle reflexes to intense sound bursts are inhibited by weak stimuli that briefly precede their elicitation. In 3 experiments, with 36 Long-Evans hooded rats, the startle stimulus (a 110-db tone burst) was presented 100 msec after the final link in a train of stimuli, the length of the train varying from 1 to 1,000, its repetition rate varying from 1 to 10 per sec, and its constituents being 40 db or 50 db white noise bursts of 25 msec duration. Inhibition was invariant across train length and repetition rate. In Exp IV, the startle stimulus was presented a variable interval after the final link, from 40 to 1,280 msec with 1 or 100 noise bursts (50 db) in the train. Inhibition developed more rapidly following the last member of the 100-stimulus train, suggesting a "priming" or sensitization effect of stimulus repetition, but its overall strength and subsequent rate of decay were not different in the 2 conditions. The general persistence of inhibition following these extended series of stimuli reveals that reflex inhibition must be the outcome of a fixed and obligatory process associated with sensory input. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overtraining and reversal learning in the rat: Effects of stimulus salience and response strategies.

Observed an overtraining reversal effect (ORE) in Exp I in 16 female hooded rats trained to discriminate horizontal from vertical stripes in the jumping stand. Overtraining was also found to produce a change in Ss' response strategy (the pattern of movements the Ss make before they jump). In Exp II, light and dark grays were the stimuli. Overtraining produced a different response strategy and no ORE was found. Results present a difficulty for the 2-stage attentional analysis of the ORE which predicts that the ORE is less likely to be found with the striped stimuli than with the gray. They provide some support, however, for a 2-stage account in which 1 stage is taken to be an overt observing response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.     

Prolactin and growth hormone mRNA and protein characterization in SMtTW rat pituitary tumours

During human pregnancy, plasma corticotrophin-releasing hormone (CRH) levels rise from undetectable amounts prior to 20 weeks gestation to reach a peak near term, with an exponential rise during the final 5 weeks of gestation. Within hours of parturition plasma levels fall and rapidly return to undetectable baseline measurements. The appearance of CRH in maternal plasma has been attributed to the placental production and subsequent release into the maternal circulation of this hormone. Previous studies have shown that human placental extracts contain a CRH-like peptide and this has been reinforced by the observation of CRH mRNA in placental tissue. Initial attempts to identify the site of production using immunocytochemistry have led to conflicting results. This study attempts to clarify this situation by using a variety of highly specific anti-CRH antibodies to show the cellular expression of placental CRH. Intense CRH staining was observed in the syncytial trophoblast layer in first trimester and term chorionic villi, whilst the underlying cytotrophoblast appeared to be negative. The fetal membranes also contained CRH immunoreactivity with the cytotrophoblast cells in the chorionic membrane displaying the most intense staining. CRH immunoactivity was also observed in the amnion and in some cells in the decidua. As a model of cellular CRH expression, cytotrophoblast cells from term chorionic membrane were isolated and shown to be positive for CRH.     

The effect of cytotoxic lesions of the hippocampus on recognition memory in the rat: Effects of stimulus size.

Rats with excitotoxic hippocampal lesions were trained on delayed nonmatching-to-sample (DNMS) with small goal boxes, containing complex objects, presented on a pseudo trial-unique schedule. A series of experiments then tested performance on repeated presentation of either the small object or large empty goal boxes. All rats acquired the nonmatching rule, but hippocampal-lesioned rats performed less well than controls on choice accuracy for the final 2 blocks of acquisition. In the study's main phase, the lesions impaired choice accuracy when the large empty boxes were used as stimuli. This deficit was ameliorated when the rats were tested with the small object boxes, although the performance of the hippocampal-lesioned rats was still below that of controls. These results extend previous reports of box size-dependent effects of hippocampal aspiration lesions on DNMS and suggest that selective damage to the hippocampus, not neuronal loss in adjacent structures or fiber tracts, is critical for the effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Insular cortex lesions and morphine-induced suppression of conditioned stimulus intake in the rat.

The present experiment examined the influence of insular cortex (IC) lesions on the intake of a taste stimulus in a consummatory procedure that used morphine as the unconditioned stimulus. In normal rats, morphine caused a rapid reduction in saccharin intake when the taste was novel but not when it was familiar. Irrespective of stimulus novelty, morphine had little influence on the saccharin consumption of IC-lesioned rats. The results are discussed in terms of a lesion-induced disruption of (i) a reward comparison mechanism and (ii) the perception of taste novelty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in discriminative stimulus and diuretic effects of the kappa opioid agonist U69,593 in the rat

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of change in video display terminal (VDT) height from desktop height (96.5 cm [38 in]) to an elevated position (109.2 cm [43 in]) on postural angles of the head and neck and the effect on cervical spine flexion moments. SUBJECTS: Twenty-seven persons (3 male, 24 female) who spent at least 3 hours per day using a computer while seated were the subjects. The subjects had a mean age of 36.7 years (SD=6.0, range=25-47). METHODS: Subjects were photographed over two 10-minute periods while seated using a computer with the VDT at two different heights. Later, a goniometer was used over images to record angles. RESULTS: There was no difference in cervical flexion moment between the two screen positions. Several postural angles of the head and neck showed changes, but the clinical relevance of these changes is questionable. CONCLUSION AND DISCUSSION: Changing the VDT height from 96.5 to 109.2 cm (floor to midscreen) has no effect on flexion moment on the cervical spine during short periods of VDT operation. If flexion moment is considered a biomechanical indicator of postural stress, it does not appear that the elevated screen position reduces postural stress on the cervical spine during short periods of VDT operation.