Search PubMed⌕ Search

PubMed · 9661986

Detecting subtle differences in behavior using waveform display analysis.

Abstract

We have devised a method, behavioral waveform display analysis, to analyze complex ethological information by measuring behavior in real time and visualizing it as a time-dependent, multistate waveform. To facilitate the generation and statistical analysis of behavioral waveform displays, we have designed a simple Macintosh-based software program. When keystrokes coded to particular behavioral states are entered in real time, this software measures and collates the time, frequency, and duration of each behavioral state. These data can then be displayed either in a tabular format for statistical analysis of behavioral duration and frequency or as graphical coordinates for creating waveform displays by direct importing into graphing programs. An illustration of the use of waveform display analysis to detect anomalous behaviors in cocaine- and amphetamine-treated mice, some of which are not detectable by a standard time-sampling assay, is shown. Both waveform display and time-sampling analysis detected drug-induced changes in sniffing, bar hanging, digging, and rearing. However, unlike time-sampling analysis, waveform display analysis also detected changes in the total duration, frequency, and average duration of these behaviors as well as additional changes in gnawing and locomotion. Additionally, visual scanning of behavioral waveform displays detected drug-induced changes in the patterns of behavior not detectable by time-sampling, including 1) a staged progression to a limited behavioral repertoire consisting of sniffing, locomotion, and rearing; 2) rapid switching between these remaining few behaviors; 3) a delayed onset of postinjection rearing relative to sniffing and locomotion; and 4) the absence of other transient stereotypies during the onset of drug action. These data indicate that behavioral waveform display provides an approach for the detection, visualization, and statistical analysis of aspects of complex behavior not amenable to detection by time-sampling methods.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

K M Campbell, R M Rohland, M J McGrath, S D Satoskar, F H Burton. 1998. Detecting subtle differences in behavior using waveform display analysis.. https://doi.org/10.1016/s0031-9384(98)00030-4

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Differentially altered mGluR1 and mGluR5 mRNA expression in rat caudate nucleus and nucleus accumbens in the development and expression of behavioral sensitization to repeated amphetamine administration.

Altered glutamatergic transmission in the striatum may be implicated in behavioral sensitization to repeated amphetamine (AMPH) administration. Quantitative in situ hybridization histochemistry was performed to define the effects of acute and chronic AMPH exposures on mRNA expression of Group I metabotropic glutamate receptors (mGluRs) in the striatum. Behavioral ratings indicated that the motor activity of rats was significantly higher after the final of five daily AMPH injections (4 mg/kg, i.p.) than that after the first of five daily AMPH, indicative of the development of behavioral sensitization. Moreover, the motor activity of rats treated with five daily AMPH was significantly greater than that of rats treated with five daily saline in response to a 2 mg/kg challenge dose of AMPH 7, 14, 28, and 60 days after the discontinuation of drug treatments, indicative of the persistent expression of behavioral sensitization. Three hours after acute administration of AMPH to naive rats, mGluR1 and mGluR5 mRNA expression in the dorsal (caudatoputamen) and ventral (nucleus accumbens) striatum showed no change as compared to acute saline injection. In rats that developed behavioral sensitization to repeated AMPH, mGluR1 levels in the dorsal and ventral striatum were increased by 53% and 43%, respectively, 3 h after the final AMPH treatment. However, this change did not persist during withdrawal since it was not observed 7, 14, and 28 days after the discontinuation of AMPH treatment. Conversely, mGluR5 levels were markedly reduced 3 h after the final of five daily AMPH treatments in the entire striatum of sensitized rats (34% and 77% of controls in the dorsal and ventral striatum, respectively). The reduction persisted at 7, 14, and 28 days of withdrawal. These results reveal a close linkage between striatal Group I mGluR gene expression and behavioral sensitization to AMPH. This may indicate functional implications of the two subtypes of Group I mGluRs in the regulation of behavioral sensitization to the dopamine stimulant.

Amphetamine↗

Regeneration of dopaminergic function in 6-hydroxydopamine-lesioned rats by neuroimmunophilin ligand treatment.

Nonimmunosuppressant immunophilin ligands have been found previously to stimulate neurite growth in culture and to promote regeneration of peripheral and central nerve fibers in vivo. To further characterize the effectiveness of these ligands, we have investigated the effect of the immunophilin ligand GPI-1046 in 6-hydroxydopamine (6-OHDA)-lesioned rats. In unlesioned rats, tetanic stimulation of the white matter induced long-term potentiation (LTP) of corticostriatal synaptic transmission as indicated by a 40-100% increase in the field potential amplitudes recorded in striatal brain slices. Unilateral microinjection of 6-OHDA into the substantia nigra resulted in a loss of corticostriatal LTP and in significant abnormality of motor behavior as assessed by amphetamine-induced ipsilateral rotations. Daily treatment of 6-OHDA-lesioned rats with GPI-1046 (10 mg/kg, s.c.) for 1 week reduced amphetamine-induced rotations by 75% and greatly restored the striatal tyrosine hydroxylase immunostaining. In addition, GPI-1046 almost completely restored corticostriatal LTP in 6-OHDA-lesioned animals. LTP in normal animals and that restored by GPI-1046 in lesioned animals were both blocked by the NMDA receptor antagonist APV, suggesting mediation by NMDA receptors. Both LTPs were sensitive to dopamine (DA) receptor antagonists. The nonselective DA receptor antagonist chlorpromazine and the selective D1-D5 receptor antagonist SCH23390 reduced the LTP by 90%. These results demonstrate that the immunophilin ligand GPI-1046 can reverse the abnormalities in the substantia nigra-striatal dopaminergic system that are caused by 6-OHDA, thus providing a potential therapeutic agent for Parkinson's disease.

Amphetamine↗

Trishomocubanes: novel sigma-receptor ligands modulate amphetamine-stimulated [3H]dopamine release.

Several trishomocubane analogues of the type 4-azahexacyclo [5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecane exhibited moderate to high affinity at sigma-receptor subtypes and low or negligible affinity at dopamine and serotonin transporters (SERT). Selected compounds were examined for their effects on amphetamine-stimulated [3H]dopamine release from striatal slices in vitro. Compounds 1, 2, 3 and 4 significantly enhanced amphetamine-stimulated release in a concentration-dependent manner. Compound 4, with the highest affinity and selectivity for the sigma(2)-receptor subtype, displayed the greatest potency. The enhancement produced by 1 and 2 was fully reversed by the selective sigma(2) antagonists 1'-[4-[1-(4-fluorophenyl)-1-H-indol-3-yl]-1-butyl]spiro[iso-benzofuran-1(3H), 4'piperidine] (Lu28-179), endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)ethyl-2-oxo-1-H-benzimidazole-1-carboxyamidehydrochloride (BIMU-8) and the non-subtype selective antagonist N-[2-(3,4-dichlorophenyl)-ethyl]-N-methyl-2-pyrrolidinyl)ethylamine (BD1008). These data suggested a potential role for compounds 1 through 4 as sigma(2)-receptor agonists in functional studies. In addition, a D(3)-trishomocubane compound 5 displayed low affinity at sigma receptors (K(i)=3 microM) and moderate affinity at dopamine transporters (K(i)=623 nM). Compound 5 significantly inhibited the potentiation mediated by compound 2, presumably through sigma(2)-receptor antagonism, or a direct action on dopamine transporters.

Amphetamine↗