J Comp Physiol A (2000) 186: 221±238 Ó Springer-Verlag 2000 REVIEW E. A. Kravitz Serotonin and aggression: insights gained from a lobster model system and speculations on the role of amine neurons in a complex behavior Accepted: 27 November 1999 Abstract The amine serotonin has been suggested to well described by other investigators, may be related to play a key role in aggression in many species of animals, the behaviors we are examining. These speculations draw including man. Precisely how the amine functions, heavily from the organizational/activational roles pro- however, has remained a mystery. As with other im- posed for steroid hormones by Phoenix et al. (1959). portant physiological questions, with their large uniquely identi®able neurons, invertebrate systems oer Key words Amine neurons á Aggression á Lobster á special advantages for the study of behavior. In this ar- Neurohormone á Serotonin ticle we illustrate that principal with a description of our studies of the role of serotonin in aggression in a lobster Abbreviations 5,7-DHT 5,7 dihydroxytryptamine á model system. Aggression is a quanti®able behavior in 5HT serotonin á A1 ®rst abdominal ganglion á crustaceans, the amine neuron systems believed to be CHH crustacean hyperglycemic hormone á important in that behavior have been completely map- CNS central nervous system á ped, and key physiological properties of an important EPSPs excitatory post synaptic potentials á subset of these neurons have been de®ned. These results IPSPs inhibitory post-synaptic potentials á are summarized here, including descriptions of the LG lateral giant axon á MG medial giant axon á ``gain-setter'' role and ``autoinhibition'' shown by these OCT octopamine á T5 ®fth thoracic ganglion neurons. Results of other investigations showing socially modulated changes in amine responsiveness at particular synaptic sites also are described. In addition, specula- Introduction tions are oered about how important developmental roles served by amines like serotonin, which have been While observing ®ghting behavior among behaviorally naõÈ ve juvenile lobsters, one cannot help but be struck by the elegance of the unfolding scene. When placed in a E. A. Kravitz new environment, animals pause, then begin to explore Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA the arena, generally keeping close to the walls, which e-mail: [email protected] they continually circle. Invariably they meet another Tel.: +1-617-432-1753; Fax: +1-617-734-7557 animal, and just as invariably, display their principal 222 weapons, the large claws. Mirroring moves, they remain the 4th stage onwards. There is no indication that this motionless, claws up, standing high on the tips of their has to be learned. That is not to say that it will not be walking legs, or they bump, darting to and fro, fore and modi®ed by experience: indeed, we already know this to aft, maintaining the display. The dactyls, the movable be the case (Scrivener 1971; Karavanich and Atema ®ngers of the claws, open wide but do not close to grasp 1998a; Rutishauser et al. 1999). Another remarkable the opponent. Meetings are short, lasting about 30 s, feature is the long-term nature of the behavioral conse- during which, in addition to the display, animals direct quences of winning and losing ®ghts. Winning animals streams of urine at each other from the nephropores at are more likely to win their next ®ght (Scrivener 1971), the base of their 2nd antennae; then they break o, only while losers are more likely to lose again. In fact, losing to begin exploring again. Few or many meetings may animals will not ®ght with any other animals, winners or take place, during each of which the display is repeated. losers of other ®ghts, for some time after their initial If a large size asymmetry exists, the ®ght ends usually ®ght. Thus, after an initial, approximately 10 min of with the smaller animal retreating then refusing to en- actual ®ghting (in an average 30-min ®ght), lobsters gage the larger in combat. A second component of dis- appear to ``remember'' the outcome for days. Challenges play may be interposed with the posturing. Here is a for investigators attempting to understand complex be- ballet, a pas de deux on the ocean ¯oor, in which one haviors like aggression, are: (1) to understand how animal advances, antennae whipping and claws folded context dependent, stereotypical, sequential pathways of downward, while the other animal retreats, antennae events, like the intensity-linked dierent levels of ®ghting straight up and claws up and open. Then on some un- behavior, are assembled in the nervous system; and (2) known cue, the animals completely switch their direc- to ®nd out where and how these systems change to allow tions of movement and the use of their appendages. If no experience to alter the subsequent ®ghting behavior. decision is reached with either of the displays, one of the As with all aspects of animal behavior, hormones and animals escalates to the next level of intensity, a move neurohormones likely serve essential roles in modulating immediately paralleled by the opponent. The transition aggression. We ®rmly believe that amines like serotonin is stepwise, seamless and irreversible. Now the weapons, (5HT) are important in aggression in crustaceans. the claws, start to be used, but only to grasp the oppo- However, amines are not the only, and may not even be nent. Like Greco-Roman wrestlers in a giant underwater the most important, hormonal substances in¯uencing arena, each combatant tries to overturn the other. If one aggression in these animals. In essentially all species of succeeds, then here too, a decision is made by the retreat animals, including man, 5HT is important in aggression of the loser. If not, ®ghts move to the next, highest level (cf. Coccaro 1989; Raleigh et al. 1991; Miczek et al. of intensity, a move almost always leading to a decision. 1994; Olivier et al. 1995; Edwards and Kravitz 1997) but Moving with great speed now, animals advance on each evidence implicates peptides like gonadotropin-releasing other with claws wide open. Their giant claws snap shut hormone and arginine vasopressin (Francis et al. 1993; on whatever they can reach, then tail ¯ips, contractions Ferris et al. 1986, 1997), and steroids like testosterone of the large abdominal ¯exor muscles, move animals (Rubinow and Schmidt 1996) in this behavior as well. back and upwards in attempts to tear their catch from Recent studies have demonstrated close interactions the opponent. The danger of damage is high now, but we between amines and peptides and the neurons involved seldom see animals losing appendages. Those that do, with these substances and circulating steroids (Asmus however, usually will not survive the continued presence and Newman 1993; Bonson et al. 1994; Mani et al. 1994; of the winner. Losers stop urinating, continually retreat, Delville et al. 1996; Ferris et al. 1997). These probably and tail ¯ip to escape the advance of the winner. foreshadow the ultimate unraveling of complex systems The ``memory'' of losing persists for many days, altering of interdigitating humoral substances, all of which the willingness of animals to engage others in combat. contribute to optimal ®ghting performance. We focus In the wild, ®ghts tend to be short in duration, with only on 5HT here, because with the exception of oc- decisions made early. Mostly these are decided by the size topamine (OCT), we have yet to positively identify other dierence that exists when two random animals meet. candidate hormones important in agonistic behavior in Under these circumstances, the making of decisions may crustaceans. We anticipate, however, that several such not have signi®cant impact on the subsequent willingness substances exist. For example, the steroid hormone to ®ght, but this remains to be established (references ecdysone, the lobster molting hormone, is one candi- for this paragraph: Scrivener 1971; Atema and Cobb date, since lobster ®ghting and escape behaviors change 1980; Huber and Kravitz 1995; Karavanich and Atema dramatically over the molt cycle (Tamm and Cobb 1978; 1998a, b; Breithaupt et al. 1999; Rutishauser et al. 1999). Cromarty et al. 1991). Levels of 20-hydroxyecdysone, One remarkable feature about ®ghting behavior in the active form of ecdysone, peak just before animals lobsters is that the entire elaborate ritual, involving show their highest levels of aggressiveness (Snyder and stereotypical stepwise increases in intensity, and appro- Chang 1991). The peptide crustacean hyperglycemic priate responses of animals to each other, all appears to hormone (CHH), a putative lobster stress hormone, is a be pre-wired in the lobster nervous system. We know second (Chang et al. 1999a). CHH-like peptides have this because the entire repertoire exists in socially naõÈ ve been localized very recently to a group of neurosecretory animals that have been raised in complete isolation from neurons whose activity is strongly in¯uenced by both 223 5HT and OCT (Chang et al. 1999b). Studies presently Drosophila (Homann 1987; Dow and von Schilcher underway in our laboratory are exploring possible 1975), powerful molecular and genetic methods in prin- linkages between the dierent hormonal systems, but the ciple allow the analysis to be brought to the level of the results are too preliminary to allow their inclusion in this genes important for the behavior (Neckameyer and article. The focus here, therefore, will be entirely on White 1992; Monasterioti et al. 1996). Our focus remains 5HT. Despite the narrow focus, we believe that useful on crustacean systems, however, because these animals generalizations and speculations can be made, that are particularly good for studies at many dierent levels should be testable, and therefore worthy of perusal. of analysis. First, lobsters and cray®sh are highly ag- The enigma of amines lies in their ubiquity.