Arousal and the control of perception and movement.

Recent discoveries on the nature of the activity generated by the reticular activating system (RAS) suggest that arousal is much more involved in perception and movement than previously thought. The RAS is not simply an amorphous, unspecific region but rather a distinct group of nuclei with specific cell and transmitter types that control waking and modulate such processes as perception and movement. Thus, disturbances in the RAS will affect a number of neurological disorders. The discovery of gamma band activity in the RAS determined that high threshold calcium channels are responsible for generating gamma band activity in the RAS. Results showing that waking is mediated by CaMKII modulation of P/Q-type channels and REM sleep is modulated by cAMP/PK modulation of N-type channels points to different intracellular pathways influencing each state. Few studies address these important breakthroughs. Novel findings also show that the same primate RAS neurons exhibiting activity in relation to arousal are also involved in locomotion. Moreover, deep brain stimulation of this region, specifically the pedunculopontine nucleus (PPN DBS), in Parkinson's disease has salutary effects on movement, sleep, and cognition. Gamma oscillations appear to participate in sensory perception, problem solving, and memory, and coherence at these frequencies may occur at cortical or thalamocortical levels. However, rather than participating in the temporal binding of sensory events, gamma band activity generated in the RAS may help stabilize coherence related to arousal, providing a stable activation state during waking, and relay such activation to the cortex. Continuous sensory input will thus induce gamma band activity in the RAS to participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our perceptions and actions. Such a role has received little attention but promises to help understand and treat a number of neurological disorders.

Cryptic speciation in the vermilion rockfish (Sebastes miniatus) and the role of bathymetry in the speciation process.

A recent phylogenetic review of the genus Sebastes suggested the existence of a cryptic species of vermilion rockfish (Sebastes miniatus). To evaluate the geographical and bathymetric range of the Type 1 and Type 2 forms reported in that study, cytochrome b sequences were examined from 548 fish. Type 1 fish were found primarily south of Point Conception on reefs deeper than 100 m. Type 2 fish were common range-wide at sites shallower than 100 m. Reproductive isolation between the two types was tested using nine microsatellite loci. Estimates of genetic divergence were made using the fixation index (F(ST)) and correspondence between haplotype and genotype was tested by Bayesian population assignment and multivariate plotting of individual genotypes. Microsatellite analyses gave strong support for the presence of two distinct groups of genotypes. All fish with Type 1 haplotypes and fish with Type 2 haplotypes from < 100 m depth had genotypes unique to their haplotype group. However, most (68%) fish with Type 2 haplotypes from > 100 m depth assigned strongly to the Type 1 genotype group. Morphometric comparisons between the two genotypic groups revealed significant differences at three of the six examined measurements. Differences in both genetics, depth of occurrence, and morphology suggest these are separate species. This observation along with evidence of depth segregation in many recent species pairs led us to hypothesize a speciation model for Sebastes spp. by which the loss or truncation of a depth-related ontogenetic migration can lead to the creation of reproductively isolated populations.

Evidence that piracetam has an anxiolytic action.

In the social interaction test of anxiety Piracetam (100 mg/kg) had an anxiolytic profile very similar to that seen after 5 days of administration of chlordiazepoxide (5 mg/kg). Piracetam (50-300 mg/kg) produced no signs of sedation and it was therefore suggested that it might be a non-sedative anxiolytic drug. Piracetam (100 mg/kg) produced significantly higher cortical concentrations of 5-hydroxytryptamine and lower concentrations of 5-hydroxyindoleacetic acid, indicating a reduced 5-HT turnover. There were no drug-induced changes in noradrenaline or dopamine in any brain region, either with or without pretreatment with alpha-methylparatyrosine. The cortical concentrations of 7 amino acids were measured and were unchanged by treatment with Piracetam.

Piracetam impairs the overshadowing of background stimuli by an informative CS.

The effects of Piracetam (100 mg/kg) on passive avoidance learning was investigated in a situation in which rats received multiple conditioning trials. The test was based on the untrained preference of rats for a dark, rather than a brightly lit compartment. After the initial black-white preference was tested, rats were restricted to the black compartment for conditioning. Different groups received different percentages of tone-shock pairings. After the conditioning trials the black-white preference was again tested. The saline-injected rats showed overshadowing of the background stimulus by the tone, in the group that had received 100% tone-shock pairings; and an acquired aversion to the background stimuli in the group that had received 0% tone-shock pairings. In the rats injected with 100 mg/kg Piracetam associative strength was partitioned indiscriminately between the tone and the background stimuli, regardless of the tone-shock pairings that had been received during conditioning.

A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants.

The effects of minor tranquilisers and of stimulant drugs were studied in the Social Interaction test of anxiety in which the illuminance and unfamiliarity of the test arena are manipulated. Acute administration of sodium phenobarbitone (25 mg/kg) was without effect. Acute administration of sodium phenobarbitone (35 mg/kg) and of meprobamate (60 mg/kg) produced sedation: both locomotor activity and social interaction were reduced. On the other hand, amphetamine sulphate (2 mg/kg) and caffeine citrate (20 mg/kg) reduced social interaction, but increased locomotor activity. Chronic administration dissociated the pattern of results produced by sodium phenobarbitone (35 mg/kg) from that produced by flurazepam (0.5 mg/kg). With chronic treatment (5 days) neither drug reduced motor activity, but whereas phenobarbitone increased social interaction regardless of the test illuminance and unfamiliarity, the increase produced by flurazepam was limited to the more stressful test conditions, i.e., when the arena was unfamiliar or brightly lit.

5,7-dihydroxytryptamine lesions of dorsal and median raphé nuclei and performance in the social interaction test of anxiety and in a home-cage aggression test.

Micro-injections of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus produced a behavioural profile in the social interaction test of anxiety similar to that seen in rats treated chronically with benzodiazepines. Neurotoxin injections into the median raphé nucleus did not produce a profile significantly different from that of the controls. In the control rats and in the rats with lesions of the median raphé nucleus, ACTH1-24 (corticotrophin) significantly reduced active social interactions, whereas it was without effect on the rats with lesions of the dorsal raphé nucleus. In the home-cage intruder test, the median raphé-lesioned rats submitted less to the intruder and stood and jumped on him more often than did the controls. The dorsal raphé-lesioned rats showed significantly fewer interactions of all kinds, compared with control rats when an intruder was placed in their home cages.

Ascending 5-HT pathways and behavioural habituation.

Microinjections of 5,7 -dihydroxytryptamine into both the dorsal and median raphe nuclei resulted in 70-85% depletions in striatal and hippocampal 5-HT concentrations but did not affect habituation of orienting in the lick-distraction test, habituation of activity in an open-field or habituation of exploration in the holeboard test. Lesioned animals were hypoactive in the latter two tests and defaecated more than control rats in the open-field suggesting an increase in emotionality or fear. Rats with selective 5,7 -dihydroxtryptamine lesions of either the dorsal or the median raphe nucleus also showed no impairment of habituation of orienting or exploration. However, median raphe lesioned animals were hyperactive at some stages of the holeboard test. In contrast to previous studies, the results suggest intact ascending 5-HT pathways are not necessary for behavioural habituation of orienting, activity or exploration. Rather, 5-HT neurones may be involved in modulation of activity or responsiveness to aversive environments.

Can social interaction be used to measure anxiety?

1 Pairs of male rats were placed in a test box for 10 min and the time they spent in active social interaction was scored. Maximum active interaction was found when the rats were tested under low light in a box with which they were familiar. When the light level was increased or when the box was unfamiliar active social interaction decreased. 2 Exploration (time spent sniffing objects) decreased in the same way in relation to test conditions as did social interaction. As these decreased, defecation, and freezing increased. 3 Anosmic controls showed that the decrease in social interaction across test conditions could not be attributed to olfactory changes in the partner. 4 Chlordiazepoxide (5 mg/kg) given chronically prevented or significantly reduced the decrease in social interaction that occurred in undrugged rats as the light level or the unfamiliarity of the test box was increased. Controls showed that this effect could not be entirely attributed to chlordiazepoxide acting selectively to increase low levels of responding. 5 The effect of chronic chlordiazepoxide contrasts with its action when given acutely; in the latter case it has only sedative effects. 6 Whether this test can be used as an animal model of anxiety is discussed and this test is compared with existing tests of anxiety.

The effects of p-chlorophenylalanine and ethanolamine-O-sulphate in an animal test of anxiety.

p-Chlorophenylalanine, which produces a depletion of brain 5-HT concentration, had effects qualitatively similar to those previously found with chronic chlordiazepoxide and with acute ethanol in the social interaction test of anxiety. This result is compatible with the idea that a reduced turnover of 5-HT is important in anxiety reduction. On the same test, ethanolamine-O-sulphate, which raises brain gamma-aminobutyric acid, was without effect, suggesting raised concentrations of this acid are not essential for anxiety reduction.