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Biomedical subjects

D A Carter

Publications and source records attributed to D A Carter.

142 records · Page 8Linked to original sources
PubMed1981

The organization of the efferent projections and striatal afferents of the entopeduncular nucleus and adjacent areas in the rat.

Multiple retrograde fluorescent tracing was employed to investigate the organization of the rat entopeduncular nucleus projections to the lateral habenula, ventral anterior-ventral lateral thalamus, parafasicular-centre median complex, and tegmenti pedunculopontis area of the brain stem. The results indicate that neurons in the rostral 2/3 of the entopeduncular nucleus project to the lateral habenula. In contrast, neurons in the caudal 1/3 of the entopeduncular nucleus project to the ventral anterior-ventral lateral thalamus, parafasicular-centre median complex, and tegmenti pedunculopontis area of the brain stem. The majority of neurons in the caudal 1/3 of the entopeduncular nucleus are retrogradely double-labeled from various combinations of tracer injections into the 3 termination areas to which they projected. Little or no retrograde labeling in the entopeduncular nucleus was produced by tracer injections in the substantia nigra or subthalamic nucleus. Only large injections of tracers in the tegmenti pedunculopontis are and the surrounding brain stem produced retrograde labeling in the entopeduncular nucleus. These brain stem injections also labeled a band of cells surrounding the entopeduncular nucleus in the zona incerta, lateral hypothalamus, of the ansa lenticularis and central nucleus of the amygdala. [3H]Leucine injections in the head of the caudate-putamen complex (but not in the cortex or globus pallidus) produced dense accumulations of silver grains over both the rostral and caudal portions of the entopeduncular nucleus. [3H]Leucine injections in the caudal body of the caudate-putamen complex produced accumulations of silver grains over a "ventral entopeduncular nucleus area' in the nucleus of the ansa peduncularis. It was suggested that the head of the striatum projects both to the neurons of the rostral "limbic' portion of the entopeduncular nucleus, which project to the lateral habenula, and to the neurons of the caudal "motor' portion of the entopeduncular nucleus, which project primarily by way of axon collaterals to the ventral anterior-ventral lateral thalamus, parafascicular-centre median complex, and tegmenti pedunculopontis area of the brain stem.

Afferent Pathways↗
PubMed1981

Feedback effects of steroids on gonadotrophin release in hyperprolactinaemic, ovariectomized rats.

The effect of hyperprolactinaemia on the progesterone-induced LH surge which occurs in oestrogen-primed, ovariectomized rats has been investigated. Hyperprolactinaemia was produced by implanting pituitary glands under the kidney capsule and levels of LH and prolactin in the circulation were measured at appropriate times during the steroid treatment. Twenty-four hours after oestrogen administration plasma LH levels were significantly reduced in both hyperprolactinaemic and sham-operated control rats. Progesterone induced a surge of LH which peaked 5 h after injection in both groups of rats. However, the peak LH level in the hyperprolactinaemic rats was less than 50% of that observed in the controls. Differences were also found in the effect of oestrogen on prolactin release in the hyperprolactinaemic rats. It is suggested that prolactin reduces the sensitivity to progesterone by a direct action on the hypothalamic-pituitary axis.

Animals↗
PubMed1981

Pituitary sensitivity to gonadotrophin releasing hormone after hyperprolactinaemia induced with neuroleptics and domperidone in the rat.

The effect of hyperprolactinaemia induced by dopamine-antagonist drugs on pituitary responsiveness to gonadotrophin releasing hormone (Gn-RH) and on plasma LH levels has been investigated in intact and ovariectomized rats. The animals were pretreated with haloperidol, pimozide or domperidone and the sensitivity of isolated pituitary glands to pulses of Gn-RH were tested using a perifusion system. Trunk blood, collected at the time of killing, was assayed for plasma LH and prolactin. In addition, a direct effect of the drugs on pituitary responsiveness to Gn-RH was investigated by perfusing pituitary glands taken from untreated, pro-oestrous rats in medium containing the dopamine antagonists. The pituitary responsiveness was significantly impaired in intact rats after treatment with each of the drugs whereas no effect was observed in pretreated ovariectomized rats. None of the drug treatments altered levels of circulating LH. High concentrations of the drugs present in the perifusion medium also inhibited pituitary responsiveness although it is not known whether the concentrations of the drugs present in the pretreated animals would exert a similar effect. The results suggest that short-term hyperprolactinaemia impairs pituitary responsiveness through a modulation of ovarian steroid secretion and that Gn-RH release is not altered. Treatment with domperidone exhibited similar effects on the parameters measured here to those caused by the two neuroleptics, indicating that this novel anti-dopaminergic drug is acting in a similar manner.

Animals↗
PubMed1979

Inhibition by pentobarbitone and urethane of the in vitro response of the adenohypophysis to luteinising hormone-releasing hormone in male rats.

1 The effect of urethane (ethyl carbamate) and sodium pentobarbitone on the luteinising hormone-releasing hormone (LH-RH)-stimulated secretion of luteinising hormone (LH) was investigated with hemipituitaries obtained from male rats and incubated in vitro. 2 Urethane and pentobarbitone were added to the incubation medium to provide final concentrations of 2.2 mg or 4 micrograms/ml and 100 micrograms or 0.1 microgram/ml respectively. The high doses of these anaesthetics blocked the LH-RH stimulated secretion of LH. The low doses significantly reduced the amounts of LH released in response to LH-RH but did not block the response completely. 3 Both concentrations of urethane reduced the basal release of LH. 4 The inhibitory action of the anaesthetics was reversible. 5 The results indicate that the two anaesthetics most commonly used in neuroendocrine experiments have a significant inhibitory action on the release of LH from the adenohypophysis.

Animals↗
PubMed1976

Differential effects of para-chlorophenylalanine on self-stimulation in caudate-putamen and lateral hypothalamus.

Rats were prepared with chronic bipolar electrodes aimed at either the caudate-putamen or lateral hypothalamus and those displaying consistent self-stimulation were given additional training at half-maximal current intensities. All subjects received an intragastric injection of para-chlorophenylalanine (400 mg/kg) and self-stimulation tests continued until pre-injection rates were re-established. Responding in both brain areas was suppressed 24 h after drug treatment. The next day, self-stimulation rates in the hypothalamus increased to 115% of pre-drug levels reaching a level of 180% by the third day of post-drug testing. In contrast, self-stimulation of sites in the neostriatum continued to decline, with minimal levels reaching 48% of control on the fourth post-drug day. Self-stimulation rates in both groups had returned to control levels by post-drug day 6. These data indicate that the role of serotonergic mechanisms in brain stimulation is locus specific, and that the specific nature of this role may be determined by interaction with other neurochemical systems. The possible interaction between dopaminergic and serotinergic mechanisms in the neostriatum is discussed as a model of self-stimulation in this region of the brain.

Animals↗
PubMed1976

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward.

Rats were implanted with electrodes in the lateral hypothalamus, put on a 22-h food deprivation schedule and trained to bar-press for ICS and for food on a CRF schedule. Haloperidol (0.08 mg/kg) and pimozide (0.22 mg/kg) significantly decreased responding for both reinforces, although responding for ICS was decreased more than it was for food. The same doses of these drugs did not decrease food consumption of a 15-min ad libitum test after 22-h of food deprivation, suggesting that the decreased bar-pressing for food was not the result of anorexia or reduced motivation for food. When similar rates of responding for ICS and for food were obtained on a V1 60 schedule, haloperidol (0.1 mg/kg) reduced responding for food and ICS to a similar extent. Thus, when baseline rate is controlled for, neuroleptics do not selectively reduce responding for ICS. In addition, examination of cumulative response records revealed that rather than producing an extinction curve, as would be predicted if neuroleptics reduced the rewarding properties of ICS, haloperidol produced a uniform decrease in the rate of responding throughout the experimental session. Similar results were obtained with intraventricular 6-hydroxydopamine (6-OHDA) injections. While these experiments do not exclude the possibility that dopaminergic (DA) systems participate in some central reinforcement mechanisms, they suggest that neuroleptics and 6-OHDA decrease responding for food or ICS primarily by impairing the function of DA systems critically involved in the initiation or maintenance of operant behaviour rather than by interfering with reward.

Animals↗
PubMed1976

Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen.

An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions.

Animals↗
PubMedDate not supplied

Comparative distribution and cardiovascular actions of substance P and substance K within the nucleus tractus solitarius of rats.

An investigation has been made into the comparative distribution and cardiovascular actions of Substance P (SP) and Substance K (SK) in the nucleus tractus solitarius (NTS) of rats. The two tachykinins were similarly distributed in the NTS region, as determined by radioimmunoassay of microdissected brain nuclei, although SP was present in an approximately 10 fold higher concentration than SK. Unilateral nodose ganglionectomy resulted in a non-significant reduction of tachykinin immunoreactivity in the ipsilateral NTS. Microinjection of synthetic SP into the NTS of urethane anaesthetised rats did not cause any significant changes in mean arterial pressure or heart rate. In contrast, SK (18 pmol) elicited a significant bradycardia which was maximal at 2 min after the injection. The bradycardic response was blocked in rats pre-treated with atropine. These results extend previous studies in which contrasting functional activities of SP and SK were demonstrated in peripheral systems, to indicate that tachykinins may exhibit different functional roles in the brain. SK, unlike SP, may be involved in central cardiovascular control via an action within the NTS.

Afferent Pathways↗
PubMedDate not supplied

Cardiovascular effects of neuropeptide Y in the nucleus tractus solitarius of rats: relationship with noradrenaline and vasopressin.

The central haemodynamic effects of neuropeptide Y (NPY), both alone and together with either noradrenaline (NA) or vasopressin (AVP), have been investigated by microinjecting synthetic peptide into the nucleus tractus solitarius (NTS) of anaesthetized rats. NPY alone elicited dose-dependent changes in blood pressure (BP) and heart rate (HR); 470 fmol inducing a pressor response, and 4.7 pmol a fall in BP. The hypotensive response to 20 nmol NA was significantly modified by both simultaneous and prior injection of an ineffective dose (47 fmol) of NPY. Prior injection of a similar dose of NPY also modified the NTS pressor effect of 10 ng AVP. A relationship between the action of AVP and NPY in the NTS was further indicated by the finding that prior injection of an ineffective dose of AVP (1 ng) reduced the hypotensive response to 4.7 pmol NPY, and by the demonstration of contrasting effects of 4.7 pmol NPY in AVP-deficient Brattleboro rats compared to parent strain LE rats. These results, taken together with the recent localization of NPY-like immunoreactivity in the NTS, suggest a role for NPY in central cardiovascular control. In addition, NPY has been shown to exhibit functional interactions with both an amine neurotransmitter and a neuropeptide present in the NTS of rats.

Animals↗
PubMedDate not supplied

alpha-MSH exhibits opioid antagonist-like effects in the brainstem of rats.

Unilateral microinjections of alpha-MSH (0.3, 1.2 and 12 pmol) into the nucleus tractus solitarius (NTS) of urethane-anaesthetized rats did not modify blood pressure or heart rate (HR). Using a dual microinjection technique, it has been shown that prior injection of alpha-MSH (0.3 pmol) attenuated the pressor effect of a similar injection of dynorphin 1-9 (18 pmol) but did not modify the cardiovascular effects of [Met]enkephalin (14 pmol). Since alpha-MSH has been localized in the NTS, the results indicate that this peptide may play a role in central cardiovascular control, possibly acting in an antagonistic manner to the endogenous opioid peptides.

Animals↗
PubMedDate not supplied

Three-dimensional structure of type IV collagen in the mammalian lens capsule.

The anterior lens capsule provides a thick, easily handled model system for the study of the organization of type IV collagen, the main component of basement membranes. We have used the technique of rapid freezing, deep-etch, and rotary replication to study the three-dimensional organization of the collagen skeleton in mammalian lens capsule after a variety of extraction procedures. In all cases the collagen appeared as a densely packed three-dimensional branching network of fine microfibrils. The organization of the microfibrils appears to show some regularity, with branch points approximately 40 nm apart. Most junctions are three-way and the network forms predominantly five-sided figures. This closely resembles the collagenous network described by Yurchenco and Ruben (1987, 1988) in human amniotic basement membrane and EHS tumor matrix, but extends their findings to another system for which X-ray diffraction data are available. The three-dimensional network is discussed in terms of molecular packing of type IV collagen in light of the information available from the diffraction data.

Animals↗