We have shown recently that the medial preoptic area (MPO) robustly innervates discrete columns along the rostrocaudal axis of the midbrain periaqueductal gray (PAG). However, the location of PAG neurons responsive to MPO activation is not known. Anterograde tract tracing was used in combination with Fos immunohistochemistry to characterize the MPO -+ PAG pathway anatomically and ,functionally within the same animal. Focal electrical or chemical stimulation of MPO in anesthetized rats induced extensive Fos expression within the PAG compared with sham controls. Fos-positive neurons were organized as 2-3 longitudinal columns. The organization and location of these columns overlapped remarkably well with the distribution of fibers and terminals in PAG labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injected into the same MPO stimulation site. This indicates that MPO inputs may terminate on the soma or proximal dendrites of neurons exhibiting elevated Fos. A second series of experiments investigated whether MPO stimulation excited PAG neurons with descending projections to the medulla. Retrograde labeling of PAG neurons projecting to the medial and lateral regions of the rostroventral medulla (RVM) was combined with MPO-induced Fos expression. The results showed that a substantial population (3743%)of Fos-positive PAG neurons projected to the ventral medulla. This indicates that MPO stimulation engages PAG-medullary output neurons. Taken together, these results suggest that the MPO + PAG + RVM projection constitutes a functional pathway. This circuit may coordinately regulate neuroendocrine, motor, and autonomic adjustments necessary for the elaboration of sexual behaviors.Key words: reproduction; antinociception; cardiovascular regulation; brainstem; sexual behavior; immunohistochemistryThe medial preoptic area (h/[PO) is a sexually dimorphic structure Simerly et al., 1984;Bloch and Gorski, 1988) that plays a pivotal role in sexual behavior and neuroendocrine function (Lisk, 1966;Powers and Valenstein, 1972;Pfaff and Sakuma, 1979;Hansen et al., 1982;Arendash and Gorski, 1983;Kalra and Kalra, 1983;Docke et al., 1984;Sachs and Meisel, 1988;Simerly et al., 1990;DonCarlos et al., 1991;Takeo et al., 1993;Hoshina et al., 1994). We recently reported that MPO robustly innervates the midbrain periaqueductal gray (PAG) (Rizvi et al., 1992) and terminates in discrete, longitudinally organized columns running through the rostrocaudal axis of PAG.PAG plays a key role in antinociception (Reynolds, 1969;Liebeskind et al., 1973;Oliveras et al., 1974;Behbehani and Fields, 1979; Lovick, 3985;Morgan and Liebeskind, 1987;Reichling et al., 1988;Lovick, 1990), cardiovascular control (Lovick, 1985;Carrive et al., 1987;Carrive et al., 1988;Carrive et al., 1989a;Lovick, 1990;Verberne and Guyenet, 1992;Murphy et al., 1994a;Murphy et al., 1995), and many of the same neuroendocrine and reproductive functions as MPO (Pfaff and SchwartzGiblin, 1988;Ogawa et al., 1991;Shipley et al., 1995). PAG neurons involved in these functions also are ...

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The midbrain periaqueductal gray (PAG) has been shown to be a site where various manipulations induce pain suppression. Recent physiological evidence (Behbehani and Pert, 1984; Behbehani et al., 1987) suggests that neurotensin has pronounced physiological actions in PAG and effects pain suppression. We have performed immunohistochemical studies in order to determine the magnitude and distribution of neurotensin-like immunoreactive (NT-IR) cell bodies and fibers in PAG. NT-IR cell bodies were common throughout PAG, although there were more in the caudal than the rostral half. NT-IR neurons were much more numerous in the ventral than the dorsal half of PAG, and some appeared to be located within the dorsal raphe nucleus. The pattern of NT-IR fibers was analyzed with the aid of image enhancement/analysis and densitometry. The fibers were found to be heterogeneously distributed, being most heavily concentrated in the region adjacent to the cerebral aqueduct in the caudal two-thirds of PAG. The distribution of NT fibers closely matches sites where exogenously applied NT elicits long-lasting excitation of PAG neurons (Behbehani et al., 1987). Based on the known physiological and behavioral actions of NT in PAG, the present anatomical results suggest that NT acts on elements located predominantly in the medial and ventrolateral parts of PAG. Neurons activated by NT may project directly to the nucleus raphe magnus and adjacent ventral medulla (Behbehani and Pert, 1984) to activate neurons that project to the spinal cord and modulate nociceptive circuits.

The effect of neurotensin (NT) on periaqueductal gray (PAG) neurons was measured with extra- and intracellular recording methods in an in vitro preparation. Neurons excited by NT were heterogeneously distributed, being preferentially located in a region of PAG rich in NT-like fiber immunoreactivity. The majority of the responsive neurons were located in regions surrounding the aqueduct and the medial part of PAG. In 90% of the neurons, application of NT produced excitation that lasted for more than 2 min, while in the remaining cells, the excitatory effect lasted for less than 1 min. An inhibitory action of NT was rarely observed. Intracellular recordings showed that NT produced a depolarization leading to an increase in the spontaneous activity and multiple spiking with only a slight decrease in membrane resistance. The excitatory effect of NT was observed in neurons that were maintained in a solution containing cobalt. These results support the hypothesis that NT action on PAG neurons is due to the depolarization of the membrane and that this effect is mediated through a postsynaptic mechanism.

In nine pentobarbital anesthetized dogs, the global effects of bupivacaine on the heart were examined during and after the onset of bupivacaine cardiotoxicity. The onset of bupivacaine cardiotoxicity was followed by the use of echocardiography to determine the sequence of events. The overall sequence of changes in the heart, demonstrated by the echocardiographic images, was markedly impaired systolic function and right ventricular dilation. The right ventricular dilation was so profound that it was associated with a septal shift into the left ventricle. Right ventricular dilation was so profound that the ability to maintain the whole ventricle within the echocardiographic image was lost. Areas obtained from the left ventricle at the two time points studied (the half-time from the beginning of injection to the occurrence of asystole referred to as midway through the toxic episode and at asystole) exhibited a significant systolic dilation only midway through the toxic episode. The mean total dose of bupivacaine resulting in the dilation of the ventricles was 14.0 +/- 3.3 mg/kg. The mean arterial pressure was reduced from control by 46.9% +/- 8.8% midway through the toxic episode. The mean pulmonary arterial pressure exhibited no significant change from before the bupivacaine injection sequence. A variety of conduction changes seen midway through the toxic episode were widening of the QRS complex, inversion, bradycardia, premature ventricular contractions (PVCs), or a combination of these. PVCs, if seen at all, were only beginning to develop and no heart block was seen in any dog midway through the toxic episode.(ABSTRACT TRUNCATED AT 250 WORDS)