Prenatal morphine exposure alters estrogen regulation of κ receptors in the cortex and POA of adult female rats but has no effects on these receptors in adult male rats

The binding characteristics of κ receptors were assessed in the frontal cortex (CX), striatum, hypothalamus, preoptic area (POA), cerebellum, and ventral tegmental area of adult male and female rats exposed prenatally to morphine or saline. Prenatal morphine exposure altered estrogen regulation of κ receptors in the CX and POA of females, but had no effects on κ receptors in any of the examined brain regions in male rats.     

Prenatal morphine exposure differentially alters TH-immunoreactivity in the stress-sensitive brain circuitry of adult male and female rats

Previously, we demonstrated that exposure to morphine during gestation increases hypothalamic norepinephrine (NE) content and turnover rate in adult male rats and decreases these measures in adult females. To investigate the basis of these alterations, the present study examined the effects of prenatal exposure to morphine on tyrosine hydroxylase immunoreactivity (TH-IR) in the brains of adult male and female progeny. In male rats, prenatal morphine exposure significantly increased the density of TH-IR in cells and fibers in the caudal paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus (LC), but had no effects in the lateral hypothalamus (LH). In female rats that were ovariectomized (OVX), prenatal morphine exposure significantly decreased the density of TH-IR in cells and fibers in the LC. Interestingly, an injection of estrogen in OVX control females reduced the mean optical density of TH-IR in the LC, but it was ineffective in drug-exposed females in the same brain region. Estrogen injections also reduced the mean optical density of TH-IR in the LH but not in the PVN of females, regardless of prenatal drug exposure. Thus, the present study suggests that prenatal morphine exposure induces long-term, sex-specific alterations in TH-IR in the PVN and LC of adult progeny.     

Prenatal exposure to morphine differentially alters gonadal hormone regulation of delta-opioid receptor binding in male and female rats

The present study tested the hypothesis that exposure to morphine on gestation days 11-18 differentially alters delta-opioid receptors in the brain of adult male and female rats. In Experiment 1, the binding characteristics of delta-opioid receptors were examined in membrane homogenates from six brain regions, including the hypothalamus (HYP), preoptic area, frontal cortex (CX), ventral tegmental area, striatum (STR) and cerebellum of adult male and female rats. In Experiment 2, the density of delta-opioid receptors was assessed in the CX and STR using receptor autoradiography. Prenatal morphine exposure has no effects on delta-opioid receptors in the brain of gonadally intact, adult male rats regardless of methodology. However, when male rats were gonadectomized in Experiment 2, morphine-exposed males have fewer delta-opioid receptors than controls in the CX but not in the STR. These reductions in cortical delta-opioid receptors are restored by testosterone replacement, demonstrating that prenatal morphine exposure alters testosterone regulation in the CX of male rats. In ovariectomized (OVX) female rats, prenatal morphine exposure increases the density of delta-opioid receptors in the frontal CX. Interestingly, this up-regulation of delta-opioid receptors is not present when the CX is investigated by autoradiography. Moreover, progesterone given alone or in combination with estrogen reduces the density of delta-opioid receptors in the CX and STR of both saline- and morphine-exposed, OVX females. Thus, mid to late gestational morphine exposure differentially alters the influence of adult gonadal hormones on delta-opioid receptors in the CX, decreasing the sensitivity in females and increasing it in males. This is also the first report to demonstrate that gonadal hormones regulate delta receptor densities in brain regions other than the HYP of OVX females.     

Prenatal nicotine exposure alters postnatal cardiorespiratory integration in young male but not female rats

The present study tested the hypothesis that prenatal nicotine exposure (PNE) induces sex specific alternations in indices of cardiorespiratory coupling during early development. Rat pups exposed to either nicotine (6 mg/kg/day) or saline (control) in utero were chronically instrumented with ECG electrodes for measurement of heart rate (HR) and respiratory frequency (RF) was monitored by whole body plethysmography on postnatal days (P)13, P16 and P26. PNE had no identifiable effect on resting respiratory frequency (RF) in either sex. There was however a strong trend (p = 0.057) for resting HR to be elevated by PNE in male offspring only. Alternatively, the HR response to hypoxia (10% O₂), was significantly blunted at P13 but significantly elevated at P26 s in the absence of any significant change in RF in PNE males only. Indicators of respiratory sinus arrhythmia (RSA) were also significantly reduced in P26 PNE males. No significant effects of PNE on HR, RF or RSA were identified in female offspring at any age. Our results demonstrate that PNE induces very specific changes in cardiorespiratory integration at select postnatal ages and these changes are more prominent in males. Additionally, alternations in cardiorespiratory integration appear to persist into later development in males only, potentially increasing the risk for cardiovascular diseases such as hypertension later in life.     

Prenatal morphine exposure differentially alters seizure susceptibility in developing female rats.

We examined the effect of prenatal morphine exposure (5-10 mg/kg on days 11-18 of gestation) on seizure susceptibility in female rats during development. The effect of morphine exposure on flurothyl-induced seizures was age-dependent. At postnatal day (PN) 15, morphine exposure decreased both clonic and tonic-clonic seizure thresholds compare to saline controls. At PN 25, morphine exposure did not alter the clonic seizure threshold but increased the threshold to tonic-clonic seizure. At PN 38, morphine exposure did not influence either threshold. The data suggest that the effects of prenatal exposure to opioids on seizures are age-related and transient.     

Prenatal exposure to morphine differentially alters gonadal hormone regulation of δ-opioid receptor binding in male and female rats

The present study tested the hypothesis that exposure to morphine on gestation days 11–18 differentially alters δ-opioid receptors in the brain of adult male and female rats. In Experiment 1, the binding characteristics of δ-opioid receptors were examined in membrane homogenates from six brain regions, including the hypothalamus (HYP), preoptic area, frontal cortex (CX), ventral tegmental area, striatum (STR) and cerebellum of adult male and female rats. In Experiment 2, the density of δ-opioid receptors was assessed in the CX and STR using receptor autoradiography. Prenatal morphine exposure has no effects on δ-opioid receptors in the brain of gonadally intact, adult male rats regardless of methodology. However, when male rats were gonadectomized in Experiment 2, morphine-exposed males have fewer δ-opioid receptors than controls in the CX but not in the STR. These reductions in cortical δ-opioid receptors are restored by testosterone replacement, demonstrating that prenatal morphine exposure alters testosterone regulation in the CX of male rats. In ovariectomized (OVX) female rats, prenatal morphine exposure increases the density of δ-opioid receptors in the frontal CX. Interestingly, this up-regulation of δ-opioid receptors is not present when the CX is investigated by autoradiography. Moreover, progesterone given alone or in combination with estrogen reduces the density of δ-opioid receptors in the CX and STR of both saline- and morphine-exposed, OVX females. Thus, mid to late gestational morphine exposure differentially alters the influence of adult gonadal hormones on δ-opioid receptors in the CX, decreasing the sensitivity in females and increasing it in males. This is also the first report to demonstrate that gonadal hormones regulate δ receptor densities in brain regions other than the HYP of OVX females.     

Prenatal morphine exposure enhances seizure susceptibility but suppresses long-term potentiation in the limbic system of adult male rats

The present study examined the effects of prenatal morphine exposure on NMDA-dependent seizure susceptibility in the entorhinal cortex (EC), and on activity-dependent synaptic plasticity at Schaffer collateral and perforant path synapses in the hippocampus. During perfusion with Mg(2+)-free ACSF, an enhancement of epileptiform discharges was found in the EC of slices from prenatally morphine-exposed male rats. A submaximal tetanic stimulation (2x50 Hz/1 s) in control slices elicited LTP at the Schaffer collateral-CA1 synapses, but neither LTP nor LTD was evoked at the perforant path-DG synapses. In slices from prenatally morphine-exposed adult male rats, long-term potentiation of synaptic transmission was not observed at Schaffer collateral-CA1 synapses, while the submaximal tetanus now elicited frank LTD of synaptic EPSPs at perforant path synapses. These data suggest that prenatal morphine exposure enhances the susceptibility of entorhinal cortex to the induction of epileptiform activity, but shifts long-term plasticity of hippocampal synapses in favor of LTD.     

Prenatal ethanol exposure alters the effects of gonadectomy on hypothalamic-pituitary-adrenal activity in male rats

Prenatal ethanol exposure has marked effects on development of the hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes. In adulthood, ethanol-treated rats show altered gonadal hormone responses and reproductive function, and increased HPA responsiveness to stressors. Importantly, prenatal ethanol differentially alters stress responsiveness in adult males and females, raising the possibility that the gonadal hormones play a role in mediating prenatal ethanol effects on HPA function. To examine a possible testicular influence on HPA activity in males, we compared the effects of gonadectomy on HPA stress responses of adult male offspring from ethanol, pair-fed (PF) and ad libitum-fed control dams. Intact ethanol-treated rats showed increased adrenocorticotrophic hormone (ACTH) but blunted testosterone and luteinising hormone (LH) responses to restraint stress, and no stress-induced elevation in arginine vasopressin (AVP) mRNA levels compared to those observed in PF and/or control rats. Gonadectomy: (i) significantly increased ACTH responses to stress in control but not ethanol-treated and PF males; (ii) eliminated differences among groups in plasma ACTH and AVP mRNA levels; and (iii) altered LH and gonadotrophin-releasing hormone responses in ethanol-treated males. Taken together, these findings suggest that central regulation of both the HPA and HPG axes are altered by prenatal ethanol exposure, with normal testicular influences on HPA function markedly reduced in ethanol-treated animals. A decreased sensitivity to inhibitory effects of androgens could contribute to the HPA hyperresponsiveness typically observed in ethanol-treated males.     

Cortical and striatal mu-opioid receptors are altered by gonadal hormone treatment but not by prenatal morphine exposure in adult male and female rats

The cerebral cortex (CX), cingulate CX (cgCX), and striatum (STR) play an important role in locomotion, cognition, emotion, and reward-motivated behaviors, and are altered by prenatal morphine exposure. We have demonstrated that delta-opioid receptors in the CX and STR of adult male and female rats are altered by prenatal morphine exposure and gonadal hormonal treatment. Because morphine binds with greater affinity to mu- than delta-opioid receptors, the present study examined the effect of prenatal morphine exposure on mu-opioid receptor density in the CX, cgCX, and STR of adult male and female rats using receptor autoradiography. In Experiment 1, three groups of adult male rats were analyzed: intact, gonadally intact; GNX, gonadectomized; and TP, GNX and testosterone propionate (TP)-treated. In Experiment 2, four groups of adult females were analyzed: OVX, ovariectomized; EB, OVX and estradiol benzoate (EB)-treated; P, OVX and progesterone (P)-treated; and EB+P, OVX and EB- and P-treated. In male rats, GNX and TP males had lower mu-opioid receptor densities in all three brain regions than gonadally intact males regardless of prenatal drug exposure. In female rats, OVX, EB+P-treated females had lower mu-opioid receptor density in the STR than OVX only females regardless of prenatal drug exposure. There were no drug or gonadal hormone effects in the CX or in the cgCX of female rats. Thus, the present study demonstrates that gonadal hormones, and not prenatal morphine exposure, alter the density of mu-opioid receptors in the CX, cgCX, and STR of adult male and female rats.     

Maternal separation alters ICSS responding in adult male and female rats, but morphine and naltrexone have little affect on that behavior

Prior research has provided evidence that the early postnatal environment can have long lasting effects on both the physiology and behavior of offspring. This is modeled in rats by using a maternal separation paradigm in which pups are separated from their mother for a few hours daily during their first two postnatal weeks. While this model has been used extensively to study stress effects and anxiety, less research has been done to examine how these separations affect measures of reward and reinforcement in adulthood. The current study investigated the impact of maternal separation (MS) on intracranial self-stimulation (ICSS) maintained responding in male and female offspring, and the effects of morphine (0.3-3.0 mg/kg) and naltrexone (0.1-10 mg/kg) on that responding. Rearing condition (MS or non-handled, NH) significantly altered response rates during acquisition in both sexes, with NH offspring exhibiting the highest rates. Group differences in baseline responding on a progressive ratio (PR-2) schedule of reinforcement were evident only in females, with MS females having response rates 50% lower than NH females. Neither morphine nor naltrexone differentially affected either rearing group. Sex impacted NH offspring: males acquired responding more readily, but females had higher response rates and breakpoints during all other phases of the experiment. In MS offspring, no sex differences were observed during acquisition, but during all other phases males had higher response rates and breakpoints than females. These results indicate that maternal separation during the first two postnatal weeks can have long-term effects on responding for ICSS, but these effects do not appear tied to endogenous opioid systems in the lateral hypothalamus.     

Multigenerational exposure to dietary nonylphenol has no severe effects on spatial learning in female rats

Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague-Dawley rats (F0) consumed soy-free diets containing 0, 25, 200 or 750 ppm nonylphenol (0, 2, 16 or 60 mg/kg per day) beginning on postnatal day (PND) 42 and continuing for two generations (F1 and F2) with breeding occurring within treatments. Females to be behaviorally tested (n = 7-8 per treatment per generation) were ovariectomized at adulthood and assessed for spatial learning and memory between PND 125-150 (young adult age). Each rat was tested for four consecutive days (three trials per day) in the Morris water maze with the platform in a fixed location. One week later, each subject was primed with estrogen and progesterone and assessed on a single day (three trials). The F1 rats continued on the same diets until PND 380-395 (middle aged) when they were re-tested as above (four consecutive days followed 1 week later with hormonal priming and a single test day). Latency to find the platform, path length and swim speed were averaged over the three trials per day and analyzed using repeated measures analyses of variance. There were no consistent effects of dietary nonylphenol exposure and no interactions of nonylphenol exposure on any measure of performance in either generation at the young age nor at the middle age in the F1 generation. When tested at the young adult age, however, hormone priming resulted in latencies and path lengths that were significantly shorter than in those exhibited during the unprimed test days, and there was no such effect when tested at middle age. Middle aged rats exhibited better performance than the same animals tested at a young age, likely as a result of familiarity and practice with the test paradigm. These data suggest that multigenerational dietary nonylphenol exposure does not cause gross alterations in Morris water maze performance in young adult or middle aged ovariectomized female rats.     

Density of mu-opioid receptors in the hippocampus of adult male and female rats is altered by prenatal morphine exposure and gonadal hormone treatment

The present in vitro autoradiography study demonstrates that prenatal exposure to morphine alters the density of mu-opioid receptors in the hippocampus of adult female but not adult male rats. Prenatal morphine exposure increased the mu-opioid receptor density in the CA1 of ovariectomized (OVX) females and in the CA3 of OVX, estradiol benzoate-plus progesterone (EB+P)-treated females, but decreased it in CA3 of OVX females. There were also hormonal effects on mu-opioid receptor density in adult female rats. In the CA1, only morphine-exposed but not saline-exposed, hormone-treated females (EB, P, or EB+P) had a decrease in mu-opioid receptor density relative to OVX females. Both saline-exposed and morphine-exposed, OVX females after gonadal hormone replacement had a lower density of mu-opioid receptors in the CA3 and in the dentate gyrus (DG) than OVX females. In male rats, there was a decrease in mu-opioid receptor density in the CA1 and CA3 of gonadectomized (GNX), testosterone 17beta-proprionate (TP)-treated males relative to GNX males regardless of prenatal morphine exposure. In the DG, the mu-opioid receptor density was reduced only in morphine-exposed but not in saline-exposed, TP-treated males compared with GNX males. Thus, our data demonstrate that mu-opioid receptor density in the hippocampus is affected by prenatal morphine exposure and by male and female gonadal hormones.     

Mu-opioid receptors in seizure-controlling brain structures are altered by prenatal morphine exposure and by male and female gonadal steroids in adult rats

The present study used autoradiography to examine the effect of prenatal morphine exposure on mu-opioid receptor density in epileptic seizure-controlling brain structures including the substantia nigra pars compacta (SNC), substantia nigra pars reticulata (SNR), superior colliculus (SC), and subthalamic nucleus (STN) of adult male and female rats. The results demonstrate that prenatal morphine exposure increases the mu-opioid receptor density in the SNC and STN, but not in the SNR or in the SC of gonadally intact adult male rats. The density of mu-opioid receptors in the SNC and STN is, however, decreased following gonadectomy in morphine-exposed males, and testosterone treatment fails to restore this decrease to the level of gonadally intact males. Further, in the SC, the density of mu receptors was lower in both saline-exposed, gonadectomized (GNX) and GNX, TP-treated males and in morphine-exposed, GNX, TP-treated males relative to gonadally intact saline- and morphine-exposed males, respectively. In ovariectomized (OVX) female rats, the same prenatal morphine exposure increases the mu-opioid receptor density in the SNC and SNR, but decreases it in the STN. The density of mu-opioid receptors is also decreased in the SNC and SC of OVX estrogen-treated females and in the SNR and SC of OVX, progesterone-treated females. Thus, the present study demonstrates that mu-opioid receptors in seizure-controlling brain structures are sex-specifically altered by prenatal morphine exposure in adult progeny. Further, prenatal morphine exposure alters gonadal hormone effects on the density of mu receptors in adult, OVX females.     

Prenatal morphine exposure alters the layer II/III pyramidal neurons morphology in lateral secondary visual cortex of juvenile rats

Altered cortical neuronal morphology and juvenle behavior manifestation by prenatal morphine exposure were well documented. However, this developmental morphine exposure affect the lateral secondary visual area (V2L), which may be critically involved in the multisensory of auditory and visual stimulus, remained poorly understood. To clarify the neuronal architecture changes possibly occurring in the V2L, Golgi‐Cox staining was used in this study to count dendritic length and the spine density of the layer II/III pyramidal neurons in the V2L of the juvenile rats (postnatal day 25, PND25) prenatally exposed to morphine (gestation days 11–18). Quantitative analysis showed that prenatal morphine exposure decreased the total length, branch number, and spine density of the layer II/III pyramidal neurons in the V2L, and selectively altered the total length of the basal dendrites but not of the apical dendrites. The findings may provide the mechanistic understanding of the behavioral changes in the children whose mothers abuse opiates during pregnancy. Synapse 63:1154–1161, 2009. © 2009 Wiley‐Liss, Inc.     

Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats

Prenatal alcohol exposure (PAE) has adverse effects on the development of numerous physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system. HPA hyper-responsiveness and impairments in immune competence have been demonstrated. The present study investigated immune function in PAE females utilizing an adjuvant-induced arthritis (AA) model, widely used as a model of human rheumatoid arthritis. Given the effects of PAE on HPA and immune function, and the known interaction between HPA and immune systems in arthritis, we hypothesized that PAE females would have heightened autoimmune responses, resulting in increased severity of arthritis, compared to controls, and that altered HPA activity might play a role in the immune system changes observed. The data demonstrate, for the first time, an adverse effect of PAE on the course and severity of AA in adulthood, indicating an important long-term alteration in functional immune status. Although overall, across prenatal treatments, adjuvant-injected animals gained less weight, and exhibited decreased thymus and increased adrenal weights, and increased basal levels of corticosterone and adrenocorticotropin, PAE females had a more prolonged course of disease and greater severity of inflammation compared to controls. In addition, PAE females exhibited blunted lymphocyte proliferative responses to concanavalin A and a greater increase in basal ACTH levels compared to controls during the induction phase, before any clinical signs of disease were apparent. These data suggest that prenatal alcohol exposure has both direct and indirect effects on inflammatory processes, altering both immune and HPA function, and likely, the normal interactions between these systems.     

Periadolescent stress exposure exerts long-term effects on adult stress responding and expression of prefrontal dopamine receptors in male and female rats

Recent research has demonstrated that experiential/environmental factors in early life can program the adult stress response in rats, and this is manifest as altered hypothalamic-pituitary-adrenocortical activity and behavior in response to a stressor. Very little work has been devoted to investigating whether the environment during adolescence plays a similar role in modulating ongoing developmental processes and how this might affect adult stress responding. Periadolescent predator odor (PPO) exposure was used here as a naturalistic model of repeated psychological stress. Behavioral and endocrine responses to PPO changed across the exposure period, and behavioral alterations persisted into adulthood. While adolescent rats showed pronounced avoidance responses upon initial PPO exposure, hyperactivity increased across the exposure period, especially in females. Corticosterone (cort) responses to stressor exposure also changed in females, with higher physiological baseline levels observed at the end of the exposure period. In adulthood, relative to rats who had received a control manipulation during adolescence, PPO-exposed rats were more fearful in a novel open field and displayed altered responses to a predator odor stress test in adulthood. Moreover, lower levels of the D2 dopamine (DA) receptor were measured in prefrontal (infralimbic and dorsopeduncular) cortices of PPO-exposed rats. These findings suggest that the adolescent period may represent a sensitive period during which developmental programming of the stress response occurs.     

Neonatal stress alters LTP in freely moving male and female adult rats

We previously reported that neonatal isolation stress significantly changes measures of hippocampal long-term potentiation (LTP) in male and female juvenile rats, i.e., at 30 days of age. The changes in dentate granule population measures, i.e., excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway, indicated that juvenile rats exposed to neonatal isolation exhibit different enhancement profiles with respect to both the magnitude and duration of LTP in a sex-specific manner. Isolated males showed a significantly greater enhancement of LTP, while female "isolates" showed significantly longer LTP duration when compared to all other groups. The present study was designed to determine whether the effects of the neonatal isolation stress paradigm endures into adulthood. Rats isolated from their mothers for 1 h per day during postnatal days 2-9 were surgically prepared at 70-90 days of age, with stimulating and recording electrodes placed in the medial perforant pathway and the hippocampal dentate gyrus, respectively. Prior to tetanization, no significant effect of sex or treatment was obtained for baseline measures of EPSP slope or PSA. In order to rule out baseline differences in hippocampal cell excitability in female adult rats, we measured the response of dentate granule cells for one estrus cycle and found no pretetanization enhancement in the evoked response in either controls or previously stressed rats. Following tetanization, there was a significant treatment and sex effect. During the induction of LTP, PSA values were significantly enhanced in both isolated males and females and had significantly longer LTP duration when compared to the unhandled control group. Additionally, we observed that females took longer to reach baseline levels than males. Taken together, these results indicate that repeated infant isolation stress enhances LTP induction and duration in both males and females. These results indicate that infant stress alters hippocampal neuroplasticity in such a way that its effect endures into adulthood.     

Prenatal exposure to SKF-38393 alters the response to light of adult rats

The current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT=zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.     

Repeated exposure to morphine alters surface expression of AMPA receptors in the rat medial prefrontal cortex

Behavioral sensitization describes the intensification of motor activity that results from repeated exposure to drugs of misuse, and the underlying neuronal adaptations are hypothesized to model aspects of the brain changes that occur in humans misusing such drugs. The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor is an ionotropic glutamate receptor involved in the neuroplasticity that accompanies acute and repeated drug administration. Changing surface expression is one means to regulate AMPA receptor function, and the present study tested the hypothesis that behavioral sensitization to the μ-opioid receptor agonist morphine is accompanied by changes in the subcellular distribution of AMPA receptors in limbic brain regions. To test this hypothesis, we used a protein cross-linking assay to assess cell surface and intracellular levels of GluA1 and GluA2 subunits in the nucleus accumbens, medial prefrontal cortex and ventral pallidum. Repeated morphine treatment decreased surface expression of GluA1 in the medial prefrontal cortex without affecting levels of GluA2. In contrast, surface levels of GluA1 or GluA2 were unchanged in the nucleus accumbens and ventral pallidum, demonstrating that although AMPA receptors in accumbal and pallidal regions are critical mediators of behaviors induced by repeated opiate exposure, these effects are not accompanied by changes in surface expression. The findings reveal that the involvement of AMPA receptor trafficking in opiate-induced behavioral sensitization is relegated to selective regions and that AMPA receptors in the medial prefrontal cortex may be particularly sensitive to these actions.     

Prenatal morphine exposure suppresses mineralocorticoid receptor-dependent basal synaptic transmission and synaptic plasticity in the lateral perforant path in adult male rats

The effects of prenatal morphine exposure (E11-18) on mineralocorticoid receptor (MR) modulation of synaptic plasticity were investigated in the lateral perforant path (LPP)-dentate gyrus granule cell synaptic system. Hippocampal slices were prepared from adult, prenatally saline- or morphine-exposed male rats. One hour prior to decapitation, some adult male rats were injected subcutaneously with saline or the MR antagonist, canrenoic acid (50 mg/kg). LPP was stimulated with high-frequency (2x100 Hz/0.5 s) and short-term plasticity (STP) and long-term potentiation (LTP) were evaluated at 5 and 30 min poststimulation, respectively. Prenatally saline-exposed male rats injected with saline 1 h prior to decapitation showed significantly higher levels of baseline, STP, and LTP than prenatally saline-exposed, canrenoic acid-treated males. In contrast, prenatally morphine-exposed male rats regardless of saline or canrenoic acid injection 1 h prior to decapitation were comparable in their baseline, STP, and LTP activities. Thus, the results demonstrate that canrenoic acid decreases the efficacy of the basal synaptic transmission in the LPP as well as suppresses synaptic plasticity in saline-exposed males. However, in adult morphine-exposed male rats, canrenoic acid has no other or further effects than a saline treatment suggesting that prenatal morphine exposure suppresses MR-dependent basal synaptic transmission as well as synaptic plasticity.