Biomedical subjects

L H Burns

Publications and source records attributed to L H Burns.

18 recordsLinked to original sources

PubMed2005

Ultra-low-dose naloxone suppresses opioid tolerance, dependence and associated changes in mu opioid receptor-G protein coupling and Gbetagamma signaling.

Opiates produce analgesia by activating mu opioid receptor-linked inhibitory G protein signaling cascades and related ion channel interactions that suppress cellular activities by hyperpolarization. After chronic opiate exposure, an excitatory effect emerges contributing to analgesic tolerance and opioid-induced hyperalgesia. Ultra-low-dose opioid antagonist co-treatment blocks the excitatory effects of opiates in vitro, as well as opioid analgesic tolerance and dependence, as was demonstrated here with ultra-low-dose naloxone combined with morphine. While the molecular mechanism for the excitatory effects of opiates is unclear, a switch in the G protein coupling profile of the mu opioid receptor and adenylyl cyclase activation by Gbetagamma have both been suggested. Using CNS regions from rats chronically treated with vehicle, morphine, morphine+ultra-low-dose naloxone or ultra-low-dose naloxone alone, we examined whether altered mu opioid receptor coupling to G proteins or adenylyl cyclase activation by Gbetagamma occurs after chronic opioid treatment. In morphine-naïve rats, mu opioid receptors coupled to Go in striatum and to both Gi and Go in periaqueductal gray and spinal cord. Although chronic morphine decreased Gi/o coupling by mu opioid receptors, a pronounced coupling to Gs emerged coincident with a Gbetagamma interaction with adenylyl cyclase types II and IV. Co-treatment with ultra-low-dose naloxone attenuated both the chronic morphine-induced Gs coupling and the Gbetagamma signaling to adenylyl cyclase, while increasing Gi/o coupling toward or beyond vehicle control levels. These findings provide a molecular mechanism underpinning opioid tolerance and dependence and their attenuation by ultra-low-dose opioid antagonists.

Adenylyl Cyclases↗

PubMed2002

Major depression in unexplained infertility.

Although a potential relationship between depression and infertility has been described throughout history, only recently has this topic been subjected to systematic investigation, and the literature is often confusing. The present study uses well-established structured psychiatric interviews--Structured Clinical Interview for DSM-III-R (SCID), Beck and Family History-Research Diagnostic Criteria (Fh-RDC)--to investigate the prevalence of major depression in a small group of women with infertility of unknown origin, and a community control sample. There were significantly more women with current depression or a history of depression in the infertile group, and of these women the majority experienced their first depressive episode prior to their diagnosis of infertility.

Adolescent↗

PubMed1999

Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine.

Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotor-stimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetamine-potentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 microg) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired during the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotor-stimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.

Animal Feed↗

PubMed1999

Effects of excitotoxic lesions of the basolateral amygdala on conditional discrimination learning with primary and conditioned reinforcement.

Rats with excitotoxic lesions of the basolateral amygdala (BLA) were not impaired in the acquisition of an appetitive visuospatial conditional discrimination between stimuli varying in temporal frequency that has previously been shown to be sensitive to the effects of lesions of the striatum and cingulate cortex. After asymptotic performance was attained, discrimination was reinforced according to a fixed ratio (FR) schedule under which n presentations of sucrose were provided following n correct responses; each correct response also being reinforced immediately by a light acting as a conditioned reinforcer. Under these conditions of reinforcement when FRn=5, BLA-lesioned rats initially showed transient impairments in several aspects of performance, but rapidly attained control levels over subsequent test sessions. No further impairments occurred when FRn=10/20. However, in various conditions of extinction, further differences in performance were revealed between the BLA-lesioned and control groups, notably a significantly enhanced resistance to extinction when both sucrose and conditioned reinforcement were omitted. The results are discussed in terms of limbic-striatal mechanisms in the control of discrimination learning and the possible role of the amygdala in the mediation of different aspects of conditioned reinforcement.

Amygdala↗

PubMed1999

The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia.

PURPOSE: Spinal cord ischemia and resulting paraplegia represent a major complication associated with surgical repair of the thoracoabdominal aorta. Although the mechanism of spinal neuronal degeneration during ischemia is unclear, it may involve excessive calcium influx via N-type voltage-sensitive calcium channels (VSCCs). The neuroprotective capacity of intrathecal (IT) administration of the selective N-type VSCC blocker ziconotide, previously shown to be potently analgesic, was studied. METHODS: In a rat aortic occlusion model, spinal cord ischemia was induced for 8, 9, or 10 minutes by occluding the descending thoracic aorta. Ziconotide was administered IT as (1) a continuous infusion of 300 or 600 ng/kg/h initiated 24 hours before ischemia and continuing an additional 24 hours or (2) a 0.3 microgram bolus injected 45 minutes before the induction of ischemia. Animals were allowed to live for 24 hours, and recovery of motor function was evaluated during this period. Spinal cords were processed using a silver impregnation technique and microtubule-associated protein type II (MAP2) immunohistochemistry. RESULTS: Continuous IT infusion of ziconotide provided significant protection against 8- and 9-minute occlusions, but not 10-minute occlusions, as indicated by recovery of motor function, degree of spinal neuronal degeneration, and loss of MAP2 immunoreactivity. Acute IT pretreatment with ziconotide provided transient protection during the initial 4 hours of reperfusion; however, this protective effect was no longer present at 24 hours. CONCLUSION: These data implicate N-type VSCC activation in spinal neuronal degeneration caused by transient spinal ischemia, because selective blockade of this channel by continuous IT infusion of ziconotide was protective against injurious intervals of spinal ischemia. Based on these findings, ziconotide may provide both neuroprotection and preemptive analgesia for aortic aneurysm surgery.

Analysis of Variance↗

PubMed1996

Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson's disease: functional recovery and graft morphology.

Neurotransplantation of human fetal dopamine (DA) neurons is currently being investigated as a therapeutic modality for Parkinson's disease (PD). However, the practical limitations of human fetal transplantation indicate a need for alternative methodologies. Using the 6-hydroxydopamine rat model of PD, we transplanted dopaminergic neurons derived from Embryonic Day 27 porcine fetuses into the denervated striatum of cyclosporine-A (CyA)-treated or non-CyA-treated rats. Functional recovery was assessed by amphetamine-induced rotation, and graft survival and morphology were analyzed using neuronal and glial immunostaining as well as in situ hybridization with a porcine repeat element DNA probe. A significant, sustained reduction in amphetamine-induced rotational asymmetry was present in the CyA-treated rats whereas the non-CyA-treated rats showed a transient behavioral recovery. The degree of rotational recovery was highly correlated to the number of surviving transplanted porcine dopaminergic neurons. TH+ neuronal survival and graft volume were significantly greater in the CyA-treated group as compared to the non-CyA group. By donor-specific neuronal and glial immunostaining as well as donor-specific DNA labeling, we demonstrate that porcine fetal neuroblasts are able to survive in the adult brain of immunosuppressed rats, mediate functional recovery, and extensively reinnervate the host striatum. These findings suggest that porcine DA neurons may be a suitable alternative to the use of human fetal tissue in neurotransplantation for PD.

Animals↗

PubMed1996

Effects of lesions to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: implication for limbic-striatal interactions.

The effects of bilateral excitotoxic lesions of 3 major sources of afferents to the ventral striatum (nucleus accumbens) were compared on an open field test of food neophobia allowing the choice between familiar and novel food. Whereas lesions of the basolateral amygdala and ventral subiculum had qualitatively similar effects to reduce food neophobia (although not affecting the latency to eat), amygdala lesions increased and the ventral subiculum decreased locomotor activity. In contrast, damage to the ventromedial prelimbic prefrontal cortex only affected initial food choice and latency measures. By comparison, excitotoxic lesions of the nucleus accumbens itself and intra-accumbens infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 increased activity and attenuated food neophobia. Results are discussed in terms of the role of limbic and prefrontal neuronal networks converging in the nucleus accumbens to control different aspects of the behavioral response to novelty.

Afferent Pathways↗

PubMed1995

Selective putaminal excitotoxic lesions in non-human primates model the movement disorder of Huntington disease.

While dyskinetic movements have been reported in primates with unilateral excitotoxic lesions following stimulation by dopaminergic agonists, the presence and intensity of the dyskinetic syndromes have varied extensively with size and location of lesion. With the intent of producing a more reliable behavioral model of Huntington disease, anatomically-defined lesions of limited size were produced by magnetic resonance imaging-guided stereotaxic injection of quinolinic acid in specific regions within the caudate and putamen of rhesus monkeys. The location and extent of the lesions were verified by magnetic resonance imaging as well as quantitative positron emission tomography imaging with the dopamine D1 specific receptor ligand SCH 39166 as a marker for striatal output neurons. The quality, frequency and duration of dyskinetic movements were assessed and quantified before and after administration of 0.5 mg/kg apomorphine in multiple test sessions over several months. Selective unilateral lesions in the posterior putamen, but not in the anterior putamen or the head of the caudate, produced marked dystonia and dyskinesia after apomorphine administration. While combined unilateral lesions of the caudate and posterior putamen produced dyskinesia similar to selective posterior putaminal lesions, combined unilateral lesions of the anterior and posterior putamen did not elicit dyskenesia. On the basis of these results, one monkey received a bilateral selective lesion in the posterior putamen. This animal remained healthy and exhibited marked spontaneous Huntington-like chorea spontaneously in the first 48 h after lesioning and persistent apomorphine-induced dyskinesia thereafter. We conclude that bilateral selective excitotoxic lesions of the posterior putamen provide an improved model of the movement disorder of Huntington disease.

Animals↗

PubMed1995

A novel mode of immunoprotection of neural xenotransplants: masking of donor major histocompatibility complex class I enhances transplant survival in the central nervous system.

To determine the role of major histocompatibility complex (MHC) class I in immunological rejection of neural xenotransplants, F(ab')2 fragments of a monoclonal antibody to porcine MHC class I were used to mask this complex on porcine fetal striatal cells transplanted into rat striata previously lesioned with quinolinic acid. Presence of MHC class I on the surface of porcine striatal cells was confirmed by fluorescence-activated cell sorting prior to F(ab')2 treatment. At three to four months post-transplantation, survival of F(ab')2-treated xenografts was assessed by means of donor-specific immunostaining and compared to that of untreated xenografts in non-immunosuppressed rats and in rats immunosuppressed with cyclosporine A. In this study, masking of donor MHC class I by F(ab')2 treatment resulted in enhanced xenografts survival compared to the non-immunosuppressed controls (graft survival rates, 52% and 7%, respectively; P < 0.005) at survival times up to four months. While xenograft survival in F(ab')2-treated animals was not significantly different from that in cyclosporine-treated rats (74% graft survival), mean graft volume in F(ab')2-treated animals was smaller than that in cyclosporine-treated animals (1.07 +/- 0.30 mm3 versus 3.14 +/- 0.51 mm3; P < 0.005). The cytoarchitectonic organization of the xenografts was similar in F(ab')2- and cyclosporine-treated animals, and grafts in both groups exhibited long distance target-directed axonal outgrowth. The pattern of immunoreactivity to porcine MHC class I in the xenografts corresponded to the regional distribution of donor glia. In xenografts undergoing rejection, infiltration with host inflammatory cells was restricted to necrotic graft remnants and spared the nearby host structures. We conclude that MHC class-I-restricted immune mechanisms play an important role in neural xenograft rejection and that masking of this complex on donor cells may provide a useful strategy for immunoprotection of neural xenografts.

Animals↗

PubMed1995

Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres.

Clinical trials are under way using fetal cells to repair damaged neuronal circuitry. However, little is known about how transplanted immature neurons can grow anatomically correct connections in the adult central nervous system (CNS). We transplanted embryonic porcine neural cells in vivo into adult rat brains with neuronal and axonal loss typical of Parkinson's or Huntington's disease. Using complementary species-specific cellular markers, we found donor axons and CD44+ astroglial fibres in host white matter tracts up to 8 mm from CNS transplant sites, although only donor axons were capable of reaching correct gray matter target regions. This work demonstrates that adult host brain can orient growth of transplanted neurons and that there are differences in transplant donor glial and axonal growth patterns in cellular repair of the mature CNS.

Animals↗

PubMed1994

Cytoarchitectonic development, axon-glia relationships, and long distance axon growth of porcine striatal xenografts in rats.

Porcine fetal lateral ganglionic eminence cells were transplanted into the quinolinic-acid-lesioned corpus striatum of immunosuppressed adult rats. The resulting grafts were analyzed for graft development with respect to donor age, donor cell dosage, and survival time from 5 to 22 weeks postimplantation. Graft development is prolonged by a factor of 3-4 times in porcine xenografts as compared to rat allografts. As grafts matured, neuronal somata developed in clusters that expressed acetylcholinesterase (AChE), tyrosine hydroxylase, and dopamine- and cAMP-associated phosphoprotein. These clusters were interspersed with AChE-poor graft regions consisting of small densely packed cells that stained for glial fibrillary acidic protein and porcine cluster of differentiation factor 44 (a species-specific glial marker). Graft axons could be selectively stained for 70-kDa neurofilament and were preferentially associated with AChE-poor, glial-rich regions in younger grafts (8 weeks), but AChE-rich neuronal regions in older grafts (22 weeks). Both graft axons and graft glial fibers projected for long distances into the host internal capsule, external capsule, corpus callosum, and anterior commissure. Donor axons also innervated host target structures including the globus pallidus and substantia nigra. This demonstrates a prolonged development of striatal cells that is appropriate to the donor species and which produces long-distance target-specific axonal growth within the adult host brain.

Animals↗

PubMed1994

Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement.

Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 micrograms d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.

Animals↗

PubMed1994

Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 impairs acquisition but not performance of discriminated approach to an appetitive CS.

The present experiments investigated the effects of blocking glutamate transmission in the amygdala on the learning and subsequent performance of a discriminated approach response to food, as well as on locomotor activity and a test of neophobia to food. In the appetitive conditioning experiment, three separate groups of rats received intra-amygdala infusions of PBS (phosphate-buffered saline) or 1.0 or 3.0 nmol of AP5, an antagonist at the NMDA glutamate receptor subtype, immediately before each conditioning session. The effects of AP5 on the performance of the discriminated approach response were tested in a fourth group of animals. AP5 dose-dependently impaired the discriminated approach response during the acquisition of the stimulus-reward association but had no effect on the performance of this response after this association was learned. These results suggest that glutamate transmission in the amygdala at the NMDA glutamate receptor subtype is important in the learning process. In separate experiments, intra-amygdala AP5 increased locomotor activity and attenuated the neophobia to food in a novel environment by increasing approaches to the food. Together, these findings parallel the effects of lesions to the basolateral amygdala. In addition, the specific effects on learning are consistent with the hypothesis that NMDA-receptor-mediated LTP underlies specific forms of learning within the amygdala.

2-Amino-5-phosphonovalerate↗

PubMed1993

Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of D-amphetamine.

The experiments reported here have investigated the impact on reward-related processes of lesioning the basolateral amygdala, ventral subiculum and prelimbic cortex which represent the major limbic sources of afferents to the ventral striatum. The results showed that, while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. However, there were important differences between the effects of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completely abolished the locomotor response to intra-accumbens infusions of D-amphetamine, in addition to blocking the potentiative effect of the same treatment on responding with conditioned reinforcement. Lesions of the basolateral amygdala, by contrast, reduced the control over behaviour by a conditioned reinforcer, but not the potentiation of that control by intra-accumbens D-amphetamine except at the highest dose. Moreover, the locomotor response to D-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected by amygdala lesions over the dose range blocked by ventral subiculum lesions. The results suggest a rather selective effect of amygdala-ventral striatal interactions on processes subserving conditioned reinforcement and a more fundamental influence of ventral subiculum-ventral striatal interactions in mediating the psychomotor stimulant effects of D-amphetamine.

Afferent Pathways↗

PubMed1993

Increased proportion of acetylcholinesterase-rich zones and improved morphological integration in host striatum of fetal grafts derived from the lateral but not the medial ganglionic eminence.

Fetal striatal grafts are found to have a modular organization revealed by acetylcholinesterase (AChE) histochemistry. The AChE-rich zones represent the only portions of these grafts that are anatomically and functionally integrated into the host brain. In this study, the medial and lateral ganglionic eminences (MGEs and LGEs) were selectively dissected from the basal telencephalon of embryonic-day-14 (E14) rat fetuses to compare their relative contributions to the AChE-rich fraction of intrastriatal grafts. Separate cell suspensions prepared from either eminence were stereotaxically implanted into excitotoxically lesioned neostriatum of adult rats. Eight weeks after transplantation, grafts of the MGE were compared with those of the LGE with respect to the proportion of AChE-rich zones, graft size, graft morphology, and afferent dopaminergic innervation as revealed by tyrosine hydroxylase (TH) immunostaining. The mean AChE-rich fraction in LGE grafts (87% +/- 4%) was markedly greater than the AChE-rich fraction in MGE grafts (25% +/- 10%). The LGE grafts were also morphologically better incorporated into the lesioned host striatum, partially reconstituting the striatal morphology. There was no statistically significant difference in graft size between the two groups. The AChE-rich LGE grafts were TH immunoreactive, whereas the AChE-poor MGE grafts were not. We conclude that grafts derived exclusively from the fetal LGE reconstitute the striatal morphology and consist almost entirely of AChE-rich zones.

Acetylcholinesterase↗

PubMed1993

Intra-nigra infusion of AMPA attenuates dopamine-dependent rotation in the rat.

It has previously been shown that glutamatergic overactivity of the subthalamic nucleus (STN) is involved in hypokinetic movement disorders such as Parkinson's disease. Conversely, it has been hypothesized that hyperkinetic behavioral syndromes may be associated with reduced glutamatergic transmission of the STN to its target areas, the substantial nigra pars reticulata (SNR) and the globus pallidus pars interna (GPI). In the present experiment, apomorphine injected systemically into unilaterally dopamine-denervated rats induced the hyperkinetic syndrome of contralateral rotation. The involvement of glutamatergic input to the SNR in this hyperkinesia was investigated by pharmacological manipulation with an agonist or an antagonist at the AMPA subtype of glutamate receptors. Either the agonist AMPA or the antagonist CNQX was infused directly into the SNR at a dose of 1.0 nmol. Intra-SNR AMPA attenuated the contralateral rotation induced by apomorphine without eliciting any effects on rotation by itself. Infusions of the antagonist CNQX did not affect either apomorphine-induced or spontaneous rotation. These results support the notion that underactivity of the SNR and its glutamatergic afferent projection from the STN may underlie hyperkinetic movement disorders and that local stimulation of the AMPA subtype of glutamate receptors can ameliorate such syndromes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1988

Neurokinin-alpha injected into the ventral tegmental area elicits a dopamine-dependent behavioral activation in the rat.

Neurokinin-alpha (NKA) and substance P (SP), neuropeptides of the tachykinin family, have been identified in dopaminergic areas of rat brain. It has previously been shown that SP microinjected into the ventral tegmental area (VTA), site of the dopaminergic A10 (DA-A10) cell bodies, causes a behavioral activation characteristic of dopamine agonists. The present experiment measured open field behavior following bilateral VTA injections of NKA (0.02, 0.2, 2.0 micrograms/0.5 microliters). NKA induced a dose-dependent behavioral activation at lower concentrations of NKA than previously reported with SP. Medium and high doses of NKA produced significant increases in locomotion and rearing in both the center and periphery of the open field. Grooming decreased with dose, although this effect was not significant. In a second experiment, the behavioral activation by NKA (2.0 micrograms) was blocked by pretreatment with haloperidol (0.2 mg/kg), confirming that the NKA-induced effect is mediated by dopamine. Although the VTA contains both SP and NKA, receptors binding NKA exist here in greater density than those binding SP. Thus NKA may be the tachykinin in this region that preferentially interacts with DA-A10 neurons mediating behavioral arousal.

Animals↗

PubMed1987

Infertility as boundary ambiguity: one theoretical perspective.

Infertility as a life event can be understood from a number of conceptual perspectives: a developmental crisis, a grief reaction, a disruption of marital contracts and roles, a crisis of identity, sexuality, and/or values, or a challenge of decision-making processes. Stress theory and the construct of boundary ambiguity can augment the understanding of the crisis of infertility by providing a different approach and unique perspective. It is the hypothesis of this article that the involuntarily childless couple may experience infertility as a stress of boundary ambiguity, that is, not knowing who is in and who is out of the family system. As infertile couples attempt to make the transition to parenthood they may experience the child they wish to have as a family member who is psychologically present but physically absent.

Adult↗