For animals in the wild, survival depends on being able to detect and respond rapidly to danger by switching from risky (e.g. conspicuous courtship) to survival-oriented behaviors. Very little is known about the hormonal or neuroendocrine mechanisms that control the rapid switch in behavioral state that occurs when an animal detects threats or other stressors. Prior studies with rough-skinned newts (Taricha granulosa), an amphibian model, found that stress-induced suppression of male sexual behaviors (amplectic clasping) involves corticosterone (CORT) and that this steroid hormone uses a novel membrane receptor and modulates the responsiveness of medullary neurons in clasp-controlling neural circuits. We provide evidence that this rapid suppression of male sex behaviors, when induced by either acute stress or CORT administration, involves activation of endocannabinoids signaling in the hindbrain. In a series of behavioral studies, administration of a cannabinoid antagonist, AM281, blocked the suppressive effects of exposure to acute stress or an injection of CORT on the performance of clasping behaviors in sexually active males. Similarly, in electrophysiological studies, prior treatment with AM281 blocked CORT-induced suppression of spontaneous neuronal activity and sensory responsiveness of hindbrain neurons in clasp-controlling neural circuits. These data suggest that, in response to acute stress, elevated CORT concentration increases endocannabinoid signaling in the hindbrain and alters sexual behaviors by modulating the excitability of medullary circuits.

A long-standing assumption about whirling disease is that the whirling pattern of swimming is caused by disequilibrium due to parasite-induced damage of the auditory-vestibular apparatus or dysfunction of the nervous system related to vertebral column damage. The behavior of rainbow trout infected with Myxobolus cerebralis as 18-d swim-up fry was studied at 90 or 240 d after parasite exposure. These fish displayed a behavioral syndrome consisting of (1) sequences of tight turns (whirling), (2) periods at rest in which the tail was elevated higher than the head, and (3) episodes of postural collapse and immobility. In spite of these behavioral disturbances, the infected fish showed virtually no behavioral indications of impaired vestibular system function, such as difficulty maintaining an upright posture. Histological examination of these infected fish revealed that parasite invasion of the skull and vertebral column was associated with granulomatous inflammation that extended into the perineural cerebrospinal-fluid-containing space, producing ring-like constrictions of the upper spinal cord and sometimes compressing and deforming the lower brain stem. In addition, some fish showed limited degeneration of pathways that connect the medulla with the spinal cord. A neurophysiological interpretation of the whirling pattern of swimming is presented, in which this abnormal behavior is proposed to result from spinal cord constriction, whereas episodes of collapse are more probably due to brain stem compression. The spinal cord and brain stem abnormalities that seem to be responsible for the abnormal behaviors in whirling disease appear to be caused largely by the invasion of granulomatous inflammation of the vertebrae and skull.

Arginine8 vasotocin (AVT), a neurohypophyseal peptide in nonmammalian vertebrates, plays a key role in the regulation of social behaviors related to reproduction. In male roughskin newts (Taricha granulosa), AVT is an important facilitator of several reproductive behaviors, including courtship clasping of females. Although AVT is known to act in certain brain regions and AVT receptors have been localized to some extent, specific target neurons for this peptide have not been identified in any species. Internalization of a receptor-specific conjugate of AVT and the fluorescent dye Oregon green was used to identify AVT target cells in the medulla of male roughskin newts. Medullary neurons are of interest because they appear to mediate facilitation of clasping by AVT. Direct application of AVT-Oregon green to the fourth ventricular surface of the medulla in vivo resulted in conjugate internalization by a widespread population of medullary neurons, particularly in the medial reticular formation and nuclei of cranial nerves V, VII, VIII, IX, and X. Some fourth-ventricle ependymal cells were also labeled. Reticulospinal neurons, which play an important role in clasping, were identified by retrograde labeling with tetramethylrhodamine dextran amine. AVT-Oregon green was internalized by 72% of these neurons. These results show that AVT can directly affect a very large and diverse medullary neuronal population, which may underlie the peptide's role in multiple neuroendocrinological processes, including autonomic and behavioral regulation. Selectivity of the AVT action may arise through interactions between AVT and steroids such as corticosterone.

The effects of neuropeptides on the brain are a major focus of neuroendocrine research, and little progress has been made in the identification of the target neurons for many neuropeptides. Arginine8-vasotocin (AVT) is a neurohypophyseal peptide present in nonmammalian vertebrates that controls many neural and behavioral functions. Here we describe synthesis and functional characterization of an AVT-Oregon green conjugate 1 (AVT-OG 1) that can be used in vivo to identify AVT target neurons. Application of AVT-OG 1 to the brainstem of an amphibian produces rapid, endosome-like internalization together with typical AVT-like neurophysiological effects. Thus, preparation of AVT-OG 1, which preserves the peptide's neurophysiological effects, is useful as a fluorescent marker for AVT target neurons. Consequently, AVT-OG 1 conjugate will have considerable utility for analyzing the neural actions of AVT in the intact brain.

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