Stimulation Of Arcuate Nucleus Research Articles

Stimulation of the hypothalamic arcuate nucleus increases brown adipose tissue nerve activity via hypothalamic paraventricular and dorsomedial nuclei.

Hypothalamic arcuate nucleus (ARCN) stimulation elicited increases in sympathetic nerve activity (IBATSNA) and temperature (TBAT) of interscapular brown adipose tissue (IBAT). The role of hypothalamic dorsomedial (DMN) and paraventricular (PVN) nuclei in mediating these responses was studied in urethane-anesthetized, artificially ventilated, male Wistar rats. In different groups of rats, inhibition of neurons in the DMN and PVN by microinjections of muscimol attenuated the increases in IBATSNA and TBAT elicited by microinjections of N-methyl-d-aspartic acid into the ipsilateral ARCN. In other groups of rats, blockade of ionotropic glutamate receptors by combined microinjections of D(-)-2-amino-7-phosphono-heptanoic acid (D-AP7) and NBQX into the DMN and PVN attenuated increases in IBATSNA and TBAT elicited by ARCN stimulation. Blockade of melanocortin 3/4 receptors in the DMN and PVN in other groups of rats resulted in attenuation of increases in IBATSNA and TBAT elicited by ipsilateral ARCN stimulation. Microinjections of Fluoro-Gold into the DMN resulted in retrograde labeling of cells in the ipsilateral ARCN, and some of these cells contained proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH), or vesicular glutamate transporter-3. Since similar projections from ARCN to the PVN have been reported by us and others, these results indicate that neurons containing POMC, α-MSH, and glutamate project from the ARCN to the DMN and PVN. Stimulation of ARCN results in the release of α-MSH and glutamate in the DMN and PVN which, in turn, cause increases in IBATSNA and TBAT.

Cardiovascular responses to microinjections of endomorphin-2 into the nucleus of the solitary tract are attenuated in the spontaneously hypertensive rat

Stimulation of µ1-opioid receptors (M1ORs) in the medial nucleus solitarius (mNTS) by endomorphin-2 (EM2) elicits decreases in mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) in Wistar rats. We tested the hypothesis that EM2-induced responses in the mNTS may be attenuated in the spontaneously hypertensive rat (SHR). Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Alterations in responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) after bilateral blockade of M1ORs in the mNTS were also studied. In SHR, microinjections of EM2 into the mNTS elicited smaller decreases in MAP, HR and GSNA compared to those elicited in WKY; smaller cardiovascular responses in SHR can be explained by lower expression of M1OR mRNA in the NTS of SHR compared to WKY. Decreases in MAP and GSNA and increases in HR were elicited by microinjections of N-methyl-d-aspartic acid (NMDA) into the ARCN of WKY. Bilateral blockade of M1ORs in the mNTS attenuated the decreases in MAP and GSNA and exaggerated the increases in HR elicited by the ARCN stimulation in WKY but not in SHR. Tonic inhibitory activity of neuropeptide Y/gamma-aminobutyric acid (NPY/GABA) neurons in the ARCN is attenuated in SHR; this observation may explain increases in MAP, GSNA and HR elicited by microinjections of NMDA into the ARCN of SHR. These results demonstrate that attenuation of EM2-induced responses in the mNTS of SHR may contribute to the excitatory responses elicited by ARCN stimulation in SHR.

Tonic γ-Aminobutyric Acid–ergic Activity in the Hypothalamic Arcuate Nucleus Is Attenuated in the Spontaneously Hypertensive Rat

We tested the hypothesis that tonic γ-aminobutyric acid–ergic activity in the hypothalamic arcuate nucleus (ARCN) modulates blood pressure control and attenuation of this inhibitory activity contributes to hypertension in the spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA) were recorded in urethane-anesthetized, artificially ventilated, adult male SHR and Wistar-Kyoto rats (WKY). Microinjections of gabazine into the ARCN elicited significantly smaller increases in MAP, HR, and GSNA in baroreceptor-intact SHR compared with baroreceptor-intact WKY. Attenuation of the responses to gabazine in SHR persisted, despite lowering of their baseline MAP to levels of WKY or barodenervation. Microinjections of N-methyl- d -aspartic acid (NMDA) into the ARCN elicited decreases in MAP and GSNA and increases in HR in baroreceptor-intact WKY. However, after microinjections of gabazine into the ARCN, microinjections of NMDA into the same nucleus elicited pressor responses in baroreceptor-intact WKY. In barodenervated WKY, increases in MAP and GSNA were elicited by ARCN stimulation by NMDA and the increases in HR were exaggerated. In baroreceptor-intact SHR, ARCN stimulation by NMDA elicited increases in MAP, GSNA, and HR which persisted, despite lowering of baseline MAP or barodenervation. Increases in MAP and GSNA elicited by ARCN stimulation by NMDA in barodenervated SHR were significantly greater than corresponding increases in barodenervated WKY. These results indicated that attenuated γ-aminobutyric acid–ergic activity in the ARCN and impaired baroreflex function may contribute to increases in blood pressure and sympathetic nerve activity after ARCN stimulation by NMDA and elevation of baseline blood pressure in SHR.

Activation of melanocortin receptors in the intermediolateral cell column of the upper thoracic cord elicits tachycardia in the rat

Melanocortin receptors (MCRs) are present in the intermediolateral cell column of the spinal cord (IML). We tested the hypothesis that activation of MCRs in the IML elicits cardioacceleratory responses and the source of melanocortins in the IML may be the melanocortin-containing neurons in the hypothalamic arcuate nucleus (ARCN). Experiments were done in urethane-anesthetized, artificially ventilated adult male Wistar rats. Microinjections (50 nl) of α-melanocyte stimulating hormone (α-MSH) (0.4-2 mM) and adrenocorticotropic hormone (ACTH) (0.5-2 mM) into the right IML elicited increases in heart rate (HR). These tachycardic responses were blocked by microinjections of melanocortin receptor 4 (MC4R) antagonists [SHU9119 (0.25 mM) or agouti-related protein (AGRP, 0.1 mM)] into the right IML. Stimulation of right ARCN by microinjections (30 nl) of N-methyl-d-aspartic acid (NMDA, 10 mM) elicited increases in HR. Blockade of MC4Rs in the ipsilateral IML at T1-T3 using SHU9119 (0.25 mM) attenuated the tachycardic responses elicited by subsequent microinjections of NMDA into the ipsilateral ARCN. ARCN neurons retrogradely labeled by microinjections of Fluoro-Gold into the right IML showed immunoreactivity for proopiomelanocortin (POMC), α-MSH, and ACTH. Fibers immunoreactive for POMC, α-MSH, and ACTH were present in the IML at T1-T3. These results indicated that activation of MC4Rs in the right IML elicited tachycardia and one of the sources of melanocortins in the IML is the ARCN. Melanocortin levels are elevated in stress and ARCN neurons are activated during stress. Our results allude to the possibility that cardiac effects of stress may be mediated via melanocortin containing ARCN neurons that project to the IML.

Baroreceptor unloading converts depressor responses elicited from the hypothalamic arcuate nucleus to pressor responses

The type of response elicited from the hypothalamic arcuate nucleus (ARCN) depends on the level of baroreceptor activity. It was hypothesized that baroreceptor unloading may determine the type of response elicited from the ARCN. This hypothesis was tested in urethane‐anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN to increases in MAP and GSNA and exaggerated tachycardia. Microinjections of ionotropic glutamate receptor antagonists into the paraventricular nucleus (PVN) in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated tachycardia. Microinjections of a melanocortin 3/4 receptor antagonist into the PVN in barodenervated rats attenuated increases in MAP, GSNA and heart rate elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alphamelanocyte stimulating hormone (alpha‐MSH) and adrenocorticotropic hormone (ACTH).Conclusionincreases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha‐MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN. Support: NIH grants HL024347 and HL076248(HNS).

Hypothalamic mTORC1 Signaling Controls Sympathetic Nerve Activity and Arterial Pressure and Mediates Leptin Effects

The fundamental importance of the hypothalamus in the regulation of autonomic and cardiovascular functions is well established. However, the molecular processes involved are not well understood. Here, we show that the mammalian (or mechanistic) target of rapamycin (mTOR) signaling in the hypothalamus is tied to the activity of the sympathetic nervous system and to cardiovascular function. Modulation of mTOR complex 1 (mTORC1) signaling caused dramatic changes in sympathetic traffic, blood flow, and arterial pressure. Our data also demonstrate the importance of hypothalamic mTORC1 signaling in transducing the sympathetic and cardiovascular actions of leptin. Moreover, we show that the PI3K pathway links the leptin receptor to mTORC1 signaling and that changes in its activity impact sympathetic traffic and arterial pressure. These findings establish mTORC1 activity in the hypothalamus as a key determinant of sympathetic and cardiovascular regulation and suggest that dysregulated hypothalamic mTORC1 activity may influence the development of cardiovascular diseases.

Effect of Barodenervation on Cardiovascular Responses Elicited from the Hypothalamic Arcuate Nucleus of the Rat

We have previously reported that chemical stimulation of the hypothalamic arcuate nucleus (ARCN) in the rat elicited increases as well as decreases in blood pressure (BP) and sympathetic nerve activity (SNA). The type of response elicited from the ARCN (i.e., increase or decrease in BP and SNA) depended on the level of baroreceptor activity which, in turn, was determined by baseline BP in rats with intact baroreceptors. Based on this information, it was hypothesized that baroreceptor unloading may play a role in the type of response elicited from the ARCN. Therefore, the effect of barodenervation on the ARCN-induced cardiovascular and sympathetic responses and the neurotransmitters in the hypothalamic paraventricular nucleus (PVN) mediating the excitatory responses elicited from the ARCN were investigated in urethane-anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN with microinjections of N-methyl-D-aspartic acid to increases in MAP and GSNA and exaggerated the increases in heart rate (HR). Combined microinjections of NBQX and D-AP7 (ionotropic glutamate receptor antagonists) into the PVN in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated increases in HR. Microinjections of SHU9119 (a melanocortin 3/4 receptor antagonist) into the PVN in barodenervated rats attenuated increases in MAP, GSNA and HR elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). It was concluded that increases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha-MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN.

Cardiovascular Responses to Chemical Stimulation of the Hypothalamic Arcuate Nucleus in the Rat: Role of the Hypothalamic Paraventricular Nucleus

The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.

Cardiovascular Responses to Hypothalamic Arcuate Nucleus Stimulation in the Rat

Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (50 nL) of N-methyl-d-aspartic acid (1, 5, and 10 mmol/L), but not artificial cerebrospinal fluid, into the hypothalamic arcuate nucleus (ARCN) elicited increases in mean arterial pressure (5.7+/-0.5, 13.2+/-1.4, and 17.3+/-1.1 mm Hg, respectively) and heart rate (24.3+/-4.3, 49.3+/-5.2, and 75.2+/-8.0 bpm, respectively). ARCN stimulation was accomplished by microinjections of a maximally effective concentration of N-methyl-d-aspartic acid (10 mmol/L). The tachycardic responses to the ARCN stimulation were significantly attenuated after bilateral vagotomy. Intrathecal injections of ionotropic glutamate receptor (iGLUR) antagonists completely blocked pressor responses to the ARCN stimulation, whereas the tachycardic responses were significantly attenuated but not abolished. Intrathecal injections of iGLUR antagonists at T9 to T10, combined with bilateral vagotomy, completely blocked the tachycardic responses to ARCN stimulation. ARCN stimulation with N-methyl-d-aspartic acid elicited increased activities of the greater splanchnic nerve (91.7+/-14.8%) and the renal nerve (109.3+/-13%). Intrathecal injections of iGLURs at T9 to T10 blocked the increase in the greater splanchnic nerve activity in response to ARCN stimulation. These results indicate the following: (1) the chemical stimulation of the ARCN elicits increases in mean arterial pressure, greater splanchnic nerve and renal nerve activity, and heart rate; (2) the increases in mean arterial pressure and sympathetic nerve activity are mediated via the activation of spinal cord iGLURs; and (3) the increases in heart rate are mediated via the activation of spinal cord iGLURs and decreases in vagal input to the heart.

The release of β-endorphin and the neuropeptide-receptor mismatch in the brain

Microprobes bearing immobilized antibodies to the carboxy-terminus of β-endorphin were used to study the release of β-endorphin in the urethane anaesthetized rat following electrical stimulation of the ipsilateral arcuate nucleus. The microprobes were inserted through the cerebral hemisphere, the superior colliculus and the midbrain periaqueductal grey. Since such microprobes detect extracellular molecules along their entire length they give information on the persistence and spread of compounds following release. Little immunoreactive- β-endorphin was detected in the areas of brain sampled during electrical stimulation of arcuate nucleus but a remarkable spread throughout the midbrain and cerebral cortex occurred within 30 min of the cessation of stimulation. The results suggest that although β-endorphin-containing fibres are absent in many parts of the brain, this neuropeptide can access receptors in these sites and it is not necessary for release to be directly adjacent to opiate receptors. As such it is important evidence supporting the hypothesis of volume transmission as a means of neuronal communication. The results also suggest that an important mechanism of the transport of β-endorphin is the cerebrospinal fluid.

Effect of electrical stimulation of arcuate nucleus on gastric electrical activity in the rats

Effect of electrical stimulation of arcuate nucleus on gastric electrical activity in the rats

Arcuate nucleus inputs onto subfornical organ neurons that respond to plasma hypernatremia and angiotensin II

Experiments were done in urethane anesthetized rats to investigate the effect of electrical and glutamate stimulation of arcuate nucleus (Arc) on the discharge rate of subfornical organ (SFO) neurons that responded to either plasma hypernatremia or angiotensin 11 (ANG 11). Extracellular recordings were made from 253 histologically verified single neurons in SFO. Of these, 40.3% (102/253) responded with excitation and 10% (25/253) with inhibition to Arc stimulation. Thirty-five (34.3%) of the units excited by Arc were also excited by intracarotid infusion of hypertonic (0.5 M) NaCl. In addition, 37 (36.3%) of the units excited by Arc were also excited by intracarotid infusion of ANG 11. Furthermore, 10 (40.0%) of the units inhibited by Arc were found to be excited by ANG 11. None of the units inhibited by Arc stimulation were responsive to plasma hypernatremia. These data indicate that inputs from Arc neurons converge onto SFO neurons that alter their discharge rate during changes in plasma concentration of Na + or ANG 11. These results suggest that Arc may be involved in body fluid balance and circulatory regulation by modulating the activity of SFO neurons that function in the detection of blood-borne signals from the depletion of intra- and extra-cellular fluid volumes.

Glutamate stimulation of arcuate nucleus inhibits responses of subfornical organ neurons to plasma hypernatremia and angiotensin II

Experiments were done in urethane anesthetized rats to investigate the effect of glutamate (Glu) stimulation of arcuate nucleus of the hypothalamus (Arc) on the discharge rate of subfornical organ (SFO) neurons during changes in plasma sodium concentration and angiotensin II (ANG II) levels. Extracellular recordings were made from 67 histologically verified single neurons within SFO. Of these, 17 (25.4%) were excited by intracarotid infusion of hypertonic NaCl and 21 (31.3%) by intracarotid ANG II infusion. Five (29.4%) of the units excited by hypertonic NaCl were also excited by Glu stimulation of Arc. Similarly, seven, (33.3%) of the units excited by ANG II were also excited by Arc stimulation. Additionally, four (19.0%) of the units excited by ANG II were inhibited by Glu stimulation of Arc. The remaining SFO units did not alter their discharge rate to activation of Arc neurons. The response of units to hypertonic NaCl or to ANG II was attenuated during simultaneous activation of Arc. These data suggest that Arc may be involved in modulating the activity of SFO neurons that function in the detection of blood-borne signals from the depletion of intra- and extracellular fluid volumes.

Lumbar intrathecal administration of naloxone antagonizes analgesia produced by electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats

In lightly pentobarbital-anesthetized and acutely-prepared rats, electrical stimulation within the arcuate nucleus of the hypothalamus consistently inhibited the tail-flick responses to noxious heating of the tail. The opioid receptor antagonist, naloxone hydrochloride applied intrathecally at the lumbar level, at dose of 20 μg, reversed this inhibition without affecting the baseline pain threshold. The same dose of naloxone, applied to the cervical subarachnoid space, had no effect on the inhibitory modulation by the arcuate nucleus. Naloxone, at doses 2- to 4-fold greater than the intrathecal dose, did not modify the suppression of the tail-flick, when given systemically. With the doses ranging from 5 to 40 μg, naloxone showed a dose-dependent blockade of the inhibition produced by stimulation of the arcuate nucleus. These results indicate that an endogenous opioid system is most likely involved in the descending inhibition of spinal nociceptive reflexes, resulting from stimulation of the arcuate nucleus of the hypothalamus.

Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats

Inhibition of noxious heat-induced tail flick by electrical stimulation of the arcuate nucleus of the hypothalamus (ARH) was examined and characterized in pentobarbital-anesthetized rats. Systematic mapping studies revealed that inhibition of the tail flick reflex could be induced by stimulating widespread areas in the ventromedial parts of the hypothalamus, which include the paraventricular nucleus, ventromedial nucleus, dorsomedial nucleus, anterior hypothalamic area as well as the ARH areas. The ARH stimulation-produced tail flick suppression could be completely blocked by systemic naloxone (2 mg/kg) which shows the involvement of an opiate mechanism in this effect. Although the tail flick reflex in the lightly anesthetized state is of significantly shorter latency than in the unanesthetized state, thresholds of the ARH stimulation for suppressing spinal nociceptive reflexes in the lightly anesthetized state were not significantly different from the thresholds at the same ARH sites in the awake state.

Peptide antagonist of delta-opioid receptor attenuates inhibition of spinal nociceptive reflex induced by stimulation of arcuate nucleus of the hypothalamus

In lightly pentobarbital-anesthetized and acutely prepared rats, electrical stimulation within the arcuate nucleus of the hypothalamus (ARH) consistently inhibited the tail-flick responses to noxious heating of the tail. The peptide ICI174864, a delta-opioid receptor antagonist applied intrathecally at the lumbar level at a dose of 1 nmol, markedly attenuated this inhibition without affecting the baseline nociceptive threshold. Normal saline injected by the same approach had no effect on the ARH inhibitory modulation. This is the first report showing an involvement of the delta-opioid receptor in the descending inhibition of spinal nociceptive reflex resulting from ARH stimulation.

Analgesic electrical stimulation of the hypothalamic arcuate nucleus: tolerance and its cross-tolerance to 2 Hz or 100 Hz electroacupuncture

Focal electrical stimulation of the arcuate nucleus of the hypothalamus (ARH) for 5 min (1 session) produced a marked elevation of tail flick latency (TFL) to noxious heat in the pentobarbital-anesthetized rat. Repeated stimulation for a total of 11 sessions at 30 min intervals resulted in a gradual decline in the hypoalgesic action, and this tolerance may last for 7 days. Tolerance to the ARH analgesic stimulation reduced the analgesia produced by low (2 Hz) but not high (100 Hz) frequency electroacupuncture (EA); and tolerance to low frequency EA analgesia attenuated the ARH stimulation-produced analgesia without affecting high frequency EA analgesia. Alternatively, rats tolerant to high-frequency EA analgesia were still sensitive to either the ARH or low-frequency EA stimulation. These results suggest that the ARH stimulation and low-frequency EA administration produced analgesia via a common neural mechanism, supporting our hypothesis put forward previously that the ARH plays an important role in mediating low- but not high-frequency EA analgesia.

Naloxone-reversible analgesia produced by microstimulation of the arcuate nucleus of the hypothalamus in pentobarbital-anesthetized rats

Suppression of the tail flick response to noxious heat and paw withdrawal response to noxious pressure were produced by electrical stimulation of arcuate nucleus of the hypothalamus (ARH) in pentobarbital anesthetized rats. Systemic administration of naloxone (2 mg/kg) greatly antagonized the ARH stimulation-produced inhibition of both algesic reflexes. The thresholds of stimulation for inhibition of two spinal nociceptive reflexes in the lightly anesthetized state were not significantly different from the thresholds of stimulation at the same ARH sites in the awake state in the same animals. These findings provide evidence establishing the (1) usefulness of the anesthetized rat model for investigation of antinociceptive mechanisms; (2) the involvement of endogenous opioid mechanisms in mediating ARH stimulation-produced analgesia.

Effects of lesion and stimulation of rat hypothalamic arcuate nucleus on the pain system

Electrolytic lesion and stimulation of the arcuate nucleus of the hypothalamus (ARH) were investigated in Wistar albino rats. 1) Discrete lesion of the ARH is followed by hyperalgesia as manifested by significantly high values of pain rating in the formalin test and by depressed analgesic effect of electroacupuncture stimulation on digastric electromyogram (dEMG) activity. 2) ARH stimulation appreciably suppressed both the responses of neurons in the lateral hypothalamus (LHA) and dEMG activity induced by tooth pulp stimulation. The suppressive influence of ARH stimulation on the responses of LHA neurons was antagonized by intraperitoneally injected and electrophoretically applied naloxone. It is thus suggested that the ARH is involved in induction or modulation of opioid-mediated analgesia.

Effects of alterations in the activity of tuberohypophysial dopaminergic neurons on the secretion of alpha-melanocyte stimulating hormone.

Administration of gamma-butyrolactone (GBL), an anesthetic which reduces dopaminergic neuronal activity, decreased the concentration of the dopamine (DA) metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the intermediate lobe of the pituitary gland, and increased alpha-melanocyte stimulating hormone (alpha MSH) concentrations in the serum of male rats. Bilateral electrical stimulation of the rostral arcuate nucleus, which contains perikarya of tuberohypophysial DA neurons, increased DOPAC concentrations in the intermediate lobe and decreased alpha MSH concentrations in the serum of GBL-anesthetized rats. Administration of the DA antagonist haloperidol prevented the decline in serum alpha MSH levels following arcuate nucleus stimulation, but had no effect on serum alpha MSH concentrations in sham-stimulated GBL-treated rats. These results indicate that GBL-induced decreases or stimulation-induced increases in the activity of tuberohypophysial DA neurons are accompanied by corresponding changes in the metabolism of DA in the intermediate lobe of the rat pituitary gland, and by reciprocal changes in the secretion of alpha MSH.