Biomedical subjects

J A Angulo

Publications and source records attributed to J A Angulo.

At least 19 recordsLinked to original sources

PubMed2006

Methamphetamine-induced cell death: selective vulnerability in neuronal subpopulations of the striatum in mice.

Methamphetamine (METH) is an illicit and potent psychostimulant, which acts as an indirect dopamine agonist. In the striatum, METH has been shown to cause long lasting neurotoxic damage to dopaminergic nerve terminals and recently, the degeneration and death of striatal cells. The present study was undertaken to identify the type of striatal neurons that undergo apoptosis after METH. Male mice received a single high dose of METH (30 mg/kg, i.p.) and were killed 24 h later. To demonstrate that METH induces apoptosis in neurons, we combined terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining with immunohistofluorescence for the neuronal marker neuron-specific nuclear protein (NeuN). Staining for TUNEL and NeuN was colocalized throughout the striatum. METH induces apoptosis in approximately 25% of striatal neurons. Cell counts of TUNEL-positive neurons in the dorsomedial, ventromedial, dorsolateral and ventrolateral quadrants of the striatum did not reveal anatomical preference. The type of striatal neuron undergoing cell death was determined by combining TUNEL with immunohistofluorescence for selective markers of striatal neurons: dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000, parvalbumin, choline acetyltransferase and somatostatin (SST). METH induces apoptosis in approximately 21% of dopamine- and cAMP-regulated phosphoprotein, of apparent Mr 32,000-positive neurons (projection neurons), 45% of GABA-parvalbumin-positive neurons in the dorsal striatum, and 29% of cholinergic neurons in the dorsal-medial striatum. In contrast, the SST-positive interneurons were refractory to METH-induced apoptosis. Finally, the amount of cell loss determined with Nissl staining correlated with the amount of TUNEL staining in the striatum of METH-treated animals. In conclusion, some of the striatal projection neurons and the GABA-parvalbumin and cholinergic interneurons were removed by apoptosis in the aftermath of METH. This imbalance in the populations of striatal neurons may lead to functional abnormalities in the output and processing of neural information in this part of the brain.

Amphetamine-Related Disorders↗

PubMed2002

Stress-induced preproenkephalin mRNA expression in the amygdala changes during early ontogeny in the rat.

Stress activates endogenous opioids that modulate nociceptive transmission. Exposure to a potentially infanticidal adult male rat suppresses pain-related behaviors in pre-weaning but not in older rats. This male-induced analgesia is mediated by l opioid receptors in the periaqueductal gray, a midbrain structure that is innervated by amygdala projections. To determine whether enkephalin, a l and d opioid receptor agonist, is activated by male exposure, mRNA levels of its precursor, preproenkephalin, were measured in subdivisions of the amygdala and the periaqueductal gray. In 14-day-old but not in 21-day-old rats, 5 min of male exposure induced analgesia to heat and increased preproenkephalin mRNA levels in the central nucleus of the amygdala but not in the periaqueductal gray. The change in the activation of enkephalinergic neurons in the central amygdala may contribute to the change in stress-induced analgesia during early ontogeny.

Aging↗

PubMed2002

Neurokinin receptors modulate the neurochemical actions of cocaine.

The psychostimulant cocaine is an indirect agonist that increases synaptic dopamine (DA) by binding with high affinity to the DA transporter (DAT) and blocking the active transport of synaptic DA back into the terminal. The resulting increase in extracellular DA alters postsynaptic activity in the circuitry of the basal ganglia. This study examines the role of neurokinin receptors on cocaine-evoked DA overflow in the striatum. Male Sprague-Dawley rats (n = 8) were treated with cocaine (10 mg/kg body weight i.p.) acutely or chronically. The pattern of DA release was assessed using in vivo microdialysis. In separate experiments two different neurokinin-1 (NK-1) receptor antagonists (D-Arg(1), D-Pro(2), D-Trp(7,9), Leu(11), or L-733,060) were perfused via the microdialysis probe for one hour in awake and freely moving animals that were subsequently injected i.p. with cocaine. Throughout the procedure, DA release was monitored at 1/2-hour intervals at a flow rate of 1 microl/min. In the groups of rats preperfused with NK-1 antagonists into the striatum, the cocaine-evoked release of DA was significantly reduced. This result suggests a significant role for the NK-1 receptor in the striatal response to acute and chronic cocaine administration.

Analysis of Variance↗

PubMed2001

Comparison of cocaine- and methamphetamine-evoked dopamine and glutamate overflow in somatodendritic and terminal field regions of the rat brain during acute, chronic, and early withdrawal conditions.

Methamphetamine and cocaine are among the most commonly abused psychostimulants. Repeated injections of psychostimulants produce behavioral sensitization or augmented locomotion in rats. Behavioral sensitization to methamphetamine and cocaine is long lasting and persists after cessation of drug treatment. Because dopamine and glutamate are major neurotransmitters of the neostriatum, we evaluated the profile of cocaine- or methamphetamine-evoked dopamine and glutamate overflow in the caudate putamen, nucleus accumbens, ventral tegmental area, and substantia nigra compacta of the rat brain. We also compared acute exposure to these drugs with chronic treatment and early withdrawal. Acute injection of methamphetamine (1 mg/kg of body weight) or cocaine (10 mg/kg) resulted in elevated levels of extracellular dopamine in all brain regions measured, although the magnitude of increase varied between brain regions. Overall, methamphetamine caused more dopamine to accumulate in the extracellular space than did cocaine when administered to animals during early withdrawal (7 days of daily injections and challenge on day 11). For example, a challenge injection of methamphetamine produced a greater elevation of extracellular dopamine in the caudate putamen when compared to acute (naïve) exposure. By contrast, a challenge injection of cocaine resulted in dopamine levels in the caudate putamen that were lower than those observed for acute exposure. In the ventral tegmental area and the substantia nigra compacta, a challenge injection of methamphetamine or cocaine resulted in extracellular dopamine levels that were lower than those for acute exposure. Thus, it appears that behavioral sensitization to cocaine can be sustained during early withdrawal in the absence of augmented drug-evoked dopamine overflow. Acute injection of methamphetamine or cocaine did not change extracellular levels of glutamate in the neostriatum. Cocaine challenge (early withdrawal) increased glutamate overflow in the caudate putamen and the nucleus accumbens. In contrast, methamphetamine challenge increased glutamate overflow in the caudate putamen, but it decreased glutamate in the nucleus accumbens. In the ventral tegmental area and the substantia nigra compacta, acute methamphetamine exposure decreased glutamate overflow, but acute cocaine exposure increased it. Although amphetamines and cocaine induce similar behavioral responses, the results presented here demonstrate that at the neurochemical level (neurotransmitter release) they sometimes evoke opposite effects depending on the brain region studied and the duration of drug treatment. Moreover, the sensitized augmentation of locomotor activity observed by us and others in response to a challenge injection of cocaine is not dependent on elevation of the extracellular concentration of dopamine in the neostriatum. We are currently investigating the hypothesis that cocaine activates peptidergic systems of the neostriatum and that these systems modulate the synaptic release of dopamine in response to psychostimulants.

Animals↗

PubMed2001

Substance P modulates cocaine-evoked dopamine overflow in the striatum of the rat brain.

To study the role of the neuropeptide substance P in modulating some of the effects of cocaine in the striatum, we administered cocaine to rats and measured preprotachykinin-A (PPT-A) messenger RNA and substance P peptide in the nigrostriatal pathway. We also measured the effect of a neurokinin-1 (NK-1) receptor antagonist on striatal cocaine-evoked dopamine overflow by in vivo microdialysis in freely moving animals. Acute administration of cocaine to naive rats (15 mg/kg of body weight) increased preprotachykinin-A mRNA levels in the dorsal and ventral aspects of the caudate putamen 4 hours after the intraperitoneal injection of cocaine. Concomitantly, in a separate group of animals, substance P peptide levels were decreased in the ventral caudate putamen and substantia nigra (38% below controls). In a separate experiment, infusion through the microdialysis probe of the neurokinin-1 receptor antagonist L-733,060 significantly decreased cocaine-evoked striatal dopamine overflow (approximately 50% inhibition at 30 minutes after cocaine administration). Taken together, these results suggest a direct role for substance P in the modulation of some of the actions of cocaine in the striatum of the rat brain.

Animals↗

PubMed2001

Neurokinin-1 receptor antagonists block acute cocaine-induced horizontal locomotion.

Systemic exposure to neurokinin-1 receptor antagonists CP099994 or LY306740 prior to cocaine administration (10 mg/kg i.p.) blocks acute, cocaine-induced horizontal locomotion. CP099994 (30 mg/kg) was delivered i.p. 30 minutes before cocaine exposure, and LY306740 (5 mg/kg) was delivered continuously by osmotic minipump for 12-14 hours before cocaine administration. These results suggest that endogenous substance P acting via neurokinin-1 receptors is necessary for the expression of acute cocaine-induced hyperactivity.

Acetamides↗

PubMed2001

Tumour necrosis factor microsatellites and HLA-DRB1, HLA-DQA1, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis.

OBJECTIVE: To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. METHODS: Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. RESULTS: TNFalpha6 showed the strongest association with disease susceptibility. The TNFalpha6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFalpha6 allele had severe disease. CONCLUSIONS: This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.

Alleles↗

PubMed1998

Sex differences in estrogenic regulation of preproenkephalin mRNA levels in the medial preoptic area of prepubertal rats.

Opioids have been implicated in sexual differentiation of the brain and in the regulation of reproductive behavior and endocrinology of mammals. Previous studies have indicated that estrogen administration in adults regulates preproenkephalin MRNA levels in several hypothalamic brain nuclei. We have determined preproenkephalin mRNA levels in estrogen-treated juvenile male and female rats to investigate the developmental pattern of estrogenic regulation of enkephalinergic neurons in the medial preoptic area. Rats were treated with estradiol benzoate (20 microgram/kg/day) or oil from day 21 to 23. Sections of the medial preoptic area (mPOA) were studied by in situ hybridization histochemistry at the single cell level and quantified with the assistance of an image analysis system. Our data indicate that males contain higher levels of preproenkephalin mRNA per neuron than females. In addition, our results indicate that estrogen causes an upward shift in the amount of mRNA expressed per cell, females demonstrating a greater response to estrogen than males. An increase in soma cell area following estrogen treatment was observed only in female mPOA enkephalinergic neurons. Taken together, these results indicate a sex difference in total preproenkephalin levels and in estrogenic regulation of preproenkephalin mRNA in the POA of juvenile rats. These results are discussed in relation to the differential role opioids may play in male and female reproductive physiology.

Animals↗

PubMed1998

Neurochemical characterization of individual vulnerability to addictive drugs in rats.

Rats exposed to a low-light, low-noise, novel environment exhibit differences in individual locomotor response to the novelty stressor. The categorization of rats in a locomotor screening procedure as low- (LR) or high-responders (HR), where LRs are in the low locomotor range while HRs belong to the high locomotor range, is significant in that HRs show higher activity in mesencephalic dopaminergic projection neurons, and also show a higher propensity to self-administer psychostimulants and other drugs of abuse compared with LRs. In this study, we examined the neurobiological basis of dopaminergic hyperactivity by comparing in HRs and LRs the steady-state differences in regulatory inputs to mesencephalic (substantia nigra and ventral tegmental area: VTA) dopaminergic neurons. In particular, using in situ hybridization, we studied levels of mRNA for tyrosine hydroxylase (TH) and cholecystokinin (CCK) in the mesencephalon, and for preprodynorphin (DYN), preproenkephalin (PPE), and preprotachykinin (PPT) in the striatum and nucleus accumbens (Acb). We also evaluated TH levels by radioimmunocytochemistry (TH-RIC) in striatal, accumbal and mesencephalic regions. HRs versus LRs had lower levels of neurochemicals belonging to the intrinsic inhibitory input to dopaminergic neurons in the VTA, e.g. lower TH-RIC (-25%) and CCK-mRNA (-48%). In contrast, HRs showed higher levels of parameters belonging to extrinsic facilitating inputs, e.g. higher PPE-mRNA (+37%). In addition, HRs had higher DYN-mRNA in Acb (+61%), which has been shown to be positively correlated with higher dopaminergic activity. These results enhance our knowledge of the neurobiological correlates of individual rats' propensities to develop drug-intake and provide some putative mechanisms for the dopaminergic hyperactivity that characterizes drug-prone animals.

Animals↗

PubMed1997

Concurrent elevation of the levels of expression of striatal preproenkephalin and preprodynorphin mRNA in the rat brain by chronic treatment with caffeine.

Caffeine is a widely consumed substance that elicits psychomotor stimulant effects and also displays addictive properties. In order to assess the effect of caffeine on striatal neuropeptide mRNA expression, male rats were injected (i.p.) with caffeine at 20, 40 or 80 mg/kg of body weight twice daily for 9 consecutive days. Preproenkephalin (PPE), preprotachykinin A (PPT-A) and preprodynorphin (PPD) mRNA levels were determined in coronal sections of brain tissue by in situ hybridization histochemistry. PPE mRNA levels were increased by chronic caffeine in all subdivisions of the striatum at 80 mg/kg (dorsolateral caudate-putamen (dlCPu), +139%; dorsomedial CPu (dmCPu), +42%; ventrolateral CPu (vlCPu), +102%; ventromedial CPu (vmCPu), +20%; and anterior CPu (aCPu), +75% relative to vehicle-injected controls that were normalized to 0% change). Similarly, PPD mRNA expression was increased in all aspects of the striatum at 80 mg/kg (dlCPu, dmCPu, vlCPu, vmCPu and aCPu, +98%, +25%, +104%, +9% and +85%, respectively). In contrast to PPE mRNA, PPD mRNA was increased +117% above control in the nucleus accumbens (NAc) at 20 mg/kg of caffeine. PPT-A mRNA expression was not significantly affected by caffeine treatment in the CPu or NAc. The data demonstrate that repeated exposure to caffeine selectively increases opioid neuropeptide mRNA expression in the striatum and the NAc of the rat brain by a dopamine-independent mechanism.

Animals↗

PubMed1997

Progressive augmentation of striatal and accumbal preprotachykinin mRNA levels by chronic treatment with methamphetamine and effect of concurrent administration of the N-methyl-D-aspartate receptor antagonist MK-801.

We have assessed the time course of repeated administration of methamphetamine (METH; 4 mg/kg) and withdrawal on the levels of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA abundance in the caudate-putamen (CPu) and nucleus accumbens (NAc) of the rat brain by in situ hybridization histochemistry. Neostriatal PPT mRNA levels rose gradually between days 1 and 6 of treatment, with the greatest elevation observed at day 6. After 6 days of daily injections twice per day, PPT mRNA increases in dorsomedial (172%) and ventromedial (196%) aspects of the CPu were significantly higher than in dorsolateral (147%) and ventrolateral (135%) subdivisions. Similarly, PPT mRNA levels were increased in the anterior CPu (163%) and NAc (121%). Concurrent administration of METH and the NMDA receptor antagonist MK-801 attenuated METH-induced increases of PPT mRNA in all aspects of the CPu at day 6 of treatment and completely prevented the increase in the NAc. Moreover, animals treated with METH for 6 days and then withdrawn for 15 days displayed PPT mRNA levels in striatum and accumbens that were statistically indistinguishable from those of controls. Adjacent sections from the same brains were used to assess PPE mRNA levels. PPE mRNA levels were transiently elevated in dorsal and ventral aspects of the CPu at day 1 and decayed to control levels at days 3 and 6. The results demonstrate that progressive treatment with methamphetamine causes stepwise elevation of preprotachykinin mRNA levels in the neostriatum. Moreover, the increase of neuropeptide mRNA shows selectivity, since PPE mRNA levels did not display progressive accumulation of message. The effects of progressive METH treatment on neostriatal PPT mRNA expression decay when the drug is withdrawn, suggesting that this neuropeptidergic system may not represent a neuroadaptation sustaining enduring sensitization to amphetamines, but may play a role in the progressive augmentation of locomotor activity elicited by this class of drug.

Animals↗

PubMed1996

Accumulation of tyrosine hydroxylase messenger RNA molecules in the rat mesencephalon by chronic caffeine treatment.

In the present study we assessed the effect of chronic treatment with caffeine on the levels of the messenger RNA molecule encoding the enzyme tyrosine hydroxylase (TH) by in situ hybridization histochemistry in the ventral tegmental area (VTA) and the substantia nigra compacta (SNc) of the rat brain. Animals that received caffeine for nine consecutive days at doses of 20, 40 and 80 mg/kg of body weight displayed increased TH mRNA levels in the SNc (up to 64% above vehicle-injected controls) and the VTA (33% above controls). Moreover, the increases observed at 80 mg/kg of caffeine were prevented by concurrent administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (0.25 mg/kg). These results demonstrate that chronic exposure to caffeine, an adenosine A2 receptor antagonist, alters the levels of expression of the mRNA encoding the rate limiting enzyme in catecholamine biosynthesis.

Animals↗

PubMed1996

Acute treatment with the N-methyl-D-aspartate receptor antagonist MK-801: effect of concurrent administration of haloperidol or scopolamine on preproenkephalin mRNA levels of the striatum and nucleus accumbens of the rat brain.

We injected rats three times at 3 h intervals (from 0900 h to 1500 h) with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 at 0.1 or 0.5 mg/kg of body weight. Three hours after the last injection, animals were sacrificed and the brains were processed for in situ hybridization histochemistry. Preproenkephalin (PPE) mRNA levels were significantly decreased throughout the caudate-putamen (CPu) and nucleus accumbens (NAc) at the lower dose. The higher dose produced significant decreases only in anterior CPu (aCPu) and NAc. Concurrent administration of the muscarinic cholinergic receptor antagonist scopolamine at 2 or 5 mg/kg neither potentiated nor prevented the effect of MK-801 on PPE mRNA levels in the neostriatum. In contrast, co-administration of haloperidol (dopamine receptor antagonist) with MK-801 blocked the effect of the latter in the NAc, and elevated PPE mRNA levels throughout the CPu. The data demonstrate that the acute effects of glutamate receptor activity on striatal and accumbal PPE mRNA expression via the NMDA receptor can be modulated by the dopaminergic system in the brain of the rat.

Animals↗

PubMed1996

Contrasting effects of repeated treatment vs. withdrawal of methamphetamine on tyrosine hydroxylase messenger RNA levels in the ventral tegmental area and substantia nigra zona compacta of the rat brain.

We have assessed the effect of repeated treatment with methamphetamine (METH) on the abundance of the messenger ribonucleic acid molecules encoding the enzyme tyrosine hydroxylase (TH) and preprocholecystokinin (PPCCK) in the substantia nigra zona compacta (SNc) and the ventral tegmental area (VTA) by in situ hybridization histochemistry. Rats were injected twice daily with METH (4 mg/kg of body weight) for 6 consecutive days and sacrificed either 5 h or 15 days after the last injection. TH mRNA in the VTA was unaffected by repeated METH treatment but was decreased 25% relative to controls in the SNc. Concurrent administration of METH and MK-801 decreased TH mRNA levels in the SNc to 47% relative to controls. In contrast, TH mRNA levels were found increased in the VTA (42%) but not SNc 15 days post-METH treatment. Coadministration of MK-801 with METH prevented the increase in TH mRNA in the VTA. PPCCK mRNA levels were not significantly affected by METH treatment in VTA or SNc either 5 h or 15 days posttreatment. The results demonstrate that exposure to repeated methamphetamine elicits changes of TH mRNA levels in the VTA that become manifest 2 weeks after withdrawal from this psychostimulant drug.

Animals↗

PubMed1995

Attenuation of neostriatal preproenkephalin and preprotachykinin mRNA abundance by chronic treatment with the kainate/quisqualate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione in the rat brain.

The present investigation assessed the effect of chronic blockade of kainate/quisqualate binding sites with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on preproenkephalin (PPE) and preprotachykinin (PPT) mRNA abundance in the neostriatum of the rat brain. Daily injection of CNQX for seven consecutive days decreased PPE mRNA abundance approximately 25% below vehicle-injected controls in dorsolateral, dorsomedial, anterior caudate-putamen (dlCPu, dmCPu and aCPu, respectively) and nucleus accumbens (NAc). Similarly, PPT mRNA abundance was significantly decreased in dlCPu, dmCPu and aCPu but not in the accumbens. The data demonstrate that non-NMDA receptor activity modulates basal levels of expression of PPE and PPT mRNAs in the neostriatum of the rat brain.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Elevation of striatal and accumbal preproenkephalin, preprotachykinin and preprodynorphin mRNA abundance subsequent to N-methyl-D-aspartate receptor blockade with MK-801.

The effect of N-methyl-D-aspartate (NMDA) receptor blockade on the expression of preproenkephalin (PPE), preprotachykinin (PPT) and preprodynorphin (PPD) mRNAs in the caudate-putamen and nucleus accumbens was assessed with the non-competitive NMDA receptor antagonist MK-801. Administration of MK-801 once daily for 7 consecutive days increased the abundance of all three neuropeptide mRNAs in the caudate-putamen (CPU) and nucleus accumbens (NAc). (1) PPE mRNA abundance was increased in the anterior CPU (26%) as well as dorsal and ventral CPU (46% and 39%, respectively) but was unaffected in the NAc. (2) PPT mRNA was increased in the NAc (33%), anterior CPU (27%), dorsal CPU (43%) and ventral CPU (67%). In the ventral CPU, PPT mRNA abundance doubled when the dose of MK-801 increased two-fold (from 67% to 119% above control). (3) PPD mRNA was elevated in dorsal and ventral regions of the CPU (49% and 24%, respectively) and in anterior CPU (50%). In the NAc PPD mRNA was increased only at the higher dose (0.1 mg/kg) of MK-801. Cellular analysis of the distribution of grains per cell shows that increases are due to increased accumulation of mRNA by previously expressing cells of the CPU and NAc. These observations demonstrate that NMDA receptor activity plays a significant role in the regulation of neuropeptide expression in the caudate-putamen and accumbens of the rat brain.

Animals↗

PubMed1994

Molecular aspects of neuropeptide regulation and function in the corpus striatum and nucleus accumbens.

In the corpus striatum and nucleus accumbens, neuropeptides participate along with conventional neurotransmitters such as dopamine, gamma-aminobutyric acid (GABA), acetylcholine and glutamate in the regulation of locomotor activity, stereotyped motor behaviors and neural events related to reward and affective state. The present review concerns itself with four major neuropeptide systems--enkephalin, dynorphin, tachykinins and neurotensin--and it summarizes neuroanatomical and functional studies as well as emphasizing regulatory interactions between neurotransmitters and neuropeptides at the level of neuropeptide gene expression. Dopaminergic transmission emanating from midbrain dopaminergic cell bodies of the substantia nigra and the ventral tegmentum regulates striatal and accumbens neuropeptide levels and their mRNAs. Evidence is presented for D1 or D2 receptor involvement as well as D1-D2 interactions that modulate neuropeptide and mRNA levels in striatum and accumbens neurons. Regulatory influences by GABAergic, serotonergic and cortical (glutamatergic) neurotransmission and via sigma receptors and circulating adrenal steroids are also described. The evidence gathered in many laboratories thus far indicates that these major basal ganglia peptidergic systems are modulated dynamically and sometimes in opposing ways by various neurochemical inputs which alter neuropeptide and neuropeptide mRNA levels over both short- and long-term. Neuropeptide systems are involved in the regulation and execution of motor programs and may also be involved in the control of mood and affect as well as self-administration behavior and behavioral sensitization, especially via the nucleus accumbens and its reciprocal connections with the midbrain, hippocampus and frontal cortex. Glucocorticoids modulate mood as well as self-administration behavior and influence locomotor activity and certain forms of stereotypy. The modulation of striatal proenkephalin and protachykinin mRNA levels by adrenal steroids is described along with distribution of adrenal steroid receptor subtypes. Adrenal steroid regulation of neuropeptide gene expression in striatum, accumbens and midbrain suggests that there may be a wider role for glucocorticoids and for other neuropeptide systems in environmental and drug influences on normal and abnormal behaviors involving the nigrostriatal and mesolimic systems.

Adrenal Cortex Hormones↗

PubMed1993

Upregulation of forebrain proenkephalin mRNA subsequent to NMDA receptor blockade.

Blockade of NMDA (N-methyl-D-aspartate) receptors for 5 h with MK 801 resulted in elevated levels of proenkephalin mRNA (up to 40% above vehicle-injected controls) in medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). Increases were dose-dependent, with maximal effect at 0.1 mg/kg (body weight). These results suggest that NMDA receptor activity exerts tonic inhibition on proenkephalin mRNA expression in the striatum and accumbens of the rat brain.

Animals↗