Ordinary language can prevent us from seeing the organization of whole-animal movement. This may be why the search for behavioral homologies has not been as fruitful as the founders of ethology had hoped. The Eshkol-Wachman (EW) movement notational system can reveal shared movement patterns that are undetectable in the kinds of informal verbal descriptions of the same behaviors that are in current use. Rules of organization that are common to locomotor development, agonistic and exploratory behavior, scent marking, play, and dopaminergic drug-induced stereotypies in a variety of vertebrates suggest that behavior progresses along a “mobility gradient” from immobility to increasing complexity and unpredictability. A progression in the opposite direction, with decreasing spatial complexity and increased stereotypy, occurs under the influence of the nonselective dopaminergic drugs apomorphine and amphetamine and partly also the selective dopamine agonist quinpirole. The behaviors associated with the mobility gradient appear to be mediated by a family of basal ganglia-thalamocortical circuits and their descending output stations. Because the small number of rules underlying the mobility gradient account for a large variety of behaviors, they may be related to the specific functional demands on these neurological systems. The EW system and the mobility gradient model should prove useful to ethologists and neurobiologists.

Studies of form-deprivation myopia (FDM) in animal models have shown that postnatal ocular growth is regulated by the quality of patterned images on the retina. One of the major challenges in myopia research is to identify the biochemical mechanisms which translate retinal visual responses into signals that regulate scleral growth. Dopamine (DA) has been implicated in this process, since retinal DA levels decline in FDM and subconjunctival injections of apomorphine (Apo, a nonspecific DA agonist) prevent FDM in a dose-dependent way (Stone et al., 1989).

To gain insight into where and how DA ligands act to regulate ocular elongation, we compared the action and distribution of DA receptor ligands injected intravitreally vs. subconjunctivally in young chicks. Ocular length was measured by A-scan ultrasound. We found that daily intravitreal injections of Apo block FDM at a 50% effective dose (ED50) of 5 pg per day, or a peak concentration in the vitreous humor of 108 pM, compared to an ED50 of 2.5 ng for subconjunctival injections as reported by Stone et al. (1989, 1990). [3H]-spiperone, a D2-receptor antagonist, reached average maximum retinal concentrations of 160 pM and 260 pM, during the first hour after intravitreal and subconjunctival administration, respectively, at the ED50 dose. In contrast, the maximum spiperone concentrations in the retinal pigment epithelium (RPE) were 30 pM and 410 pM, respectively, after intravitreal or subconjunctival ED50 doses. Spiperone concentrations in sclera after ED50 doses to the two sites differed by 4 x 104 (0.4 pM vs. 1.7 nM, respectively). The FDM-preventing action of Apo was blocked completely by simultaneous administration of spiperone but not by SCH 23390 (a D1-receptor antagonist) in 100-fold molar excess.

These results show that apomorphine acts to prevent FDM at an intraocular site, presumably in retina and/or pigment epithelium, but not sclera, whether administered intravitreally or subconjunctivally. A dose yielding a concentration of 100–260 pM, delivered ≤1 h per day, produces half-maximal inhibition. This action is mediated by D2-receptors, for which the dissociation constant for apomorphine is ≤1 nM. The retinal pigment epithelium may act as a trophic relay station, responding to a retinal messenger which may be DA and secreting scleral growth-regulator(s) from its basal surface.

Subthalamic nucleus (STN) neurons have a pivotal role in basal ganglia, as a result of their intrinsic membrane properties, connections within the circuit and glutamatergic nature. Their innate pacemaker activity, consisting of a single-spike tonic mode of discharge, is abolished in the case of hemiballism, profoundly disrupted in the Parkinsonian state and replaced by a regular bursting mode under treatment (high-frequency stimulation, HFS). We propose that control STN activity represents a clock, an internal measure of time allowing the correct automatic execution of learned movements and, in particular, the automatic switch from one movement to the next in a sequential motor pattern. STN neuronal activity would be able to reset the frequency of oscillations of motor thalamo-cortical loops, notably in the γ band.

The dopaminergic agonist apomorphine hydrochloride (0.1, 0.2 and 0.4 mg s.c.) compared to placebo in a double-blind, latin square design induced yawing in population of 8 healthy volunteers. Yawning was the only behavioral effect observed and was not dose-related, as all the 3 doses were equipotent. Yawning was maximum between 10 and 20 min post-injection and did not last longer than 20 min. Compared to the data in the literature, 0.1 mg is the lowest dose described as inducing yawning in man. Further studies using doses lower than 0.1 mg would be required to determine the highest inactive dose in order to use apomorphine-induced yawning as an index of CNS dopaminergic receptor sensitivity.

In order to further assess the alterations which might underly behavioral deficits associated with a reduced dopaminergic transmission, the effects of apomorphine at doses thought to stimulate dopaminergic autoreceptors were studied on rat operant behavior.

Low doses of apomorphine caused a reward deficit when animais were shifted from continuons reinforcement to fixed ratio schedules of food delivery (fig. 1). This effect could be accounted for by a decreased ability of secondary reinforcers to sustain responding and/or by a disruption of cognitive processes (Table 1). The apomorphine-induced reward deficit in the fixed ratio 4 schedule was reversed by “disinhibitory” neuroleptics including amisulpride, pimozide, pipotiazine and sulpiride, at low to moderate doses. Conversely, “conventional” neuroleptics such as chlorpromazine, fluphenazine, haloperidol, metoclopramide and thioridazine were found inactive in reversing the deficit caused by apomorphine (fig. 2). Results obtained after lesion of dopaminergic neurons by 6-hydroxydopamine suggested that the behavioral deficit induced by apomorphine was related not so much to a reduction in dopaminergic activity in given restricted areas such as the VTA (fig. 3), the nucleus accumbens (fig. 4) or the prefrontal cortex (fig. 5), as to a functional imbalance between mesolimbic and mesocortical dopaminergic systems.