Body temperature-dependent and independent actions of chlordimeform on visual evoked potentials and axonal transport in optic system of rat.

Pattern-reversal-evoked potentials (PREPs), flash-evoked potentials (FEPs), rapid axonal transport in the optic system and body temperature were measured in hooded rats, treated with either saline or the formamidine insecticide/acaricide, chlordimeform (CDM). Rats receiving chlordimeform had low body temperatures when housed at standard laboratory room temperature, 22 degrees C, but not at 30 degrees C. Peak latencies of flash-evoked potentials were prolonged by chlordimeform at 22 degrees C, but not at 30 degrees C. The rate of axonal transport was slowed in chlordimeform-treated hypothermic rats, but not in chlordimeform-treated warmed rats. These findings suggest that the flash-evoked potential and axonal transport changes produced by chlordimeform were an indirect consequence of hypothermia. In contrast, chlordimeform increased pattern-reversal evoked potential peak latencies and peak-to-peak amplitudes independent of body temperature. These findings confirm and extend previous reports of chlordimeform-induced hypothermia, emphasize the importance of changes in body temperature as a possible confounding factor in studies of neuroactive agents and demonstrate that chlordimeform has both body-temperature-dependent and independent actions in the visual system in the rat.

Monoamine oxidase inhibition cannot account for changes in visual evoked potentials produced by chlordimeform.

Chlordimeform (CDM), a formamidine insecticide and monoamine oxidase (MAO) inhibitor, has recently been shown to produce large changes in visual evoked potentials of hooded rats (Boyes and Dyer, 1984a). Two experiments were performed to determine if the changes in evoked potentials were a result of the inhibition of MAO. In the first, the degree of inhibition of MAO in the brains of rats treated with chlordimeform (1.0-100 mg/kg, i.p.) was compared with that produced by pargyline (0.3-30 mg/kg, i.p.). Both compounds preferentially inhibited MAO-B, although MAO-A was substantially inhibited at larger doses. Pargyline was a relatively more potent inhibitor of MAO than chlordimeform, but not more efficacious. In the second experiment, pattern reversal evoked potentials (PREPs) and flash-evoked potentials (FEPs) were recorded from groups of rats after treatment with either saline, 0.4 mg/kg pargyline, 20 mg/kg pargyline or 40 mg/kg chlordimeform. The latter two groups were selected so as to have similar levels of inhibition of MAO, about 90% inhibition of MAO-B and 60% inhibition of MAO-A. The results showed a doubling of the amplitude of pattern reversal evoked potentials and increased latencies of the pattern reversal evoked potential and the flash-evoked-potentials in the chlordimeform-treated group, but no significant changes from saline control values in the pargyline-treated groups. These results confirm that chlordimeform is a MAO inhibitor at doses which produce behavioral and electrophysiological changes, but demonstrate further that the changes in visual evoked potentials produced by chlordimeform are not a direct result of the inhibition of MAO.

Acute treatment with trimethyltin alters alcohol self-selection.

Male rats of the Long-Evans strain were divided into two equal groups of nine each and given either 7.0 mg/kg trimethyltin (TMT) or 0.9% saline by intragastric gavage. The pattern of self-selection of alcohol in concentrations of 3%--30% was examined in both groups at 21 and 150 days following the gavage. The TMT-treated rat consistently drank less alcohol than did the controls at every concentration of alcohol. This difference in alcohol intake was equally significant when the rats were tested in a food-contingent, schedule-induced polydipsia situation. Further, although the TMT-lesioned animal consumed fewer calories per day in the form of alcohol, their overall daily caloric intakes were slightly higher than those of the controls. These results are interpreted as a consequence of damage to structures of the forebrain and as part of a syndrome of behavioral and neurological pathology.

Time-dependent neurobiological effects of colchicine administered directly into the hippocampus of rats.

Rats were given bilateral injections of colchicine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken, up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acoustic startle reactivity, and accelerated acquisition of two-way shuttle box avoidance, but did not affect reactivity to a noxious thermal stimulus. Measurement of dynorphin in the hippocampus indicated that colchicine rapidly depleted this neuropeptide, which is thought to be contained preferentially in the mossy fibers of granule cells of the hippocampus. Colchicine also decreased Met-enkephalin in the hippocampus, but the magnitude of the change (22%) was less than that (89% depletion) observed for hippocampal dynorphin. Examination of hippocampal morphology using light microscopic techniques indicated that colchicine caused approximately 60% degeneration of granule cells in the hippocampus. Although the length of the pyramidal cells was decreased (12-16%), the width of the CA1 and CA3 region of the hippocampus was not affected. These data underscore the importance of the granule cells in the mediation of behavioral processes such as motor activity, startle reactivity and performance of shuttle box avoidance.

Ontogeny of flash-evoked potentials in unanesthetized rats.

The effects of age and stimulation frequency (0.2/sec, 1.0/sec, 2.0/sec, or 4.0/sec) on flash-evoked potentials (FEPs) were investigated in awake, unsedated, unrestrained rats. Animals were tested daily from postnatal day (PND) 8 to PND 20, and every 3 or 4 days thereafter until PND 41. On PND 9, a single negative wave (N1a) was observed following 0.2/sec flash presentation. Animals tested on PND 10 exhibited a positive wave (P2) following the return of peak N1a to baseline. On PND 13 another negative wave (N1) appeared on the leading shoulder of peak N1a. Peak N1 became the dominant negative wave on PND 14. Peak N1a merged into N1 and had disappeared by PND 19. Peak N3 was first observed as a negative shift following peak P2 on PND 15. Peaks N2 and P3 were not observed in the group average waveforms until PND 34. Peak latencies decreased through the fifth postnatal week. Peak amplitudes increased with age until after eye opening (PND 15), but were variable thereafter. No FEPs were observed following higher than 0.2/sec flash presentation until PND 13. Increasing stimulation frequency decreased N1 and P2 peak amplitudes, but had no effect on peak latencies.

Possible role of the brainstem in the mediation of prepulse inhibition in the rat.

Bilateral stimulation of electrodes aimed at the cuneiform nucleus produced significant inhibition of the startle response produced by presentation of an 8-kHz, 110-dB tone. Stimulation of electrodes aimed at the deep mesencephalic nucleus also reduced the magnitude of the startle response, but the effect was less than that following stimulation sites near the cuneiform nucleus. Histological reconstruction of the electrode tip locations revealed a significant negative correlation between the maximum magnitude reduction of the acoustic startle response following an electrical prepulse stimulus and the distance from the cuneiform nucleus. Histological examination also indicated that some electrodes aimed at the cuneiform nucleus were located in or near the inferior colliculus or parabrachial nucleus, all of which are thought to be part of an inhibitory circuit parallel to the acoustic startle reflex arc. These experiments support the view that the prepulse inhibition of the acoustic startle reflex originates in the brainstem.

Amygdaloid kindling increases enkephalin-like immunoreactivity but decreases dynorphin-A-like immunoreactivity in rat hippocampus.

The effects of amygdaloid kindling on the regional levels and distribution of enkephalin-like and dynorphin-A (DN)-like immunoreactivity (LI) were examined. One day after completion of kindling, radioimmunoassay revealed a 71% decrease in DN1-8-LI and a 43% increase in [Met5]-enkephalin-LI in the hippocampus. Immunostaining revealed a depletion of DN1-17-LI in the hippocampal mossy fiber pathway and an increase in [Leu5]-enkephalin-LI in the temporoammonic pathway. Four weeks after completion of kindling, the levels and immunostaining intensity of dynorphin and enkephalin in the hippocampus had returned to control values.

Superior colliculus lesions and flash evoked potentials from rat cortex.

It is generally assumed that the primary response of the rat flash evoked potential (FEP) is activated by a retino-geniculate path, and that the secondary response reflects input to the cortex by way of the superior colliculus (SC) or other brainstem structures. In the present study, male Long-Evans rats were implanted with monopolar screw electrodes placed over the left visual cortex, and a pair of twisted monopolar depth electrodes, which were used to produce electrolytic lesions, were placed in each SC. One half of the animals did not receive the electrolytic treatment (controls). FEP waveforms were obtained from all animals prior to treatment, and 2 and 5 days after treatment. Histological analysis was performed to verify electrode placement and determine lesion size. Electrolytic lesions resulting in massive destruction of the SC produced no decrement in any portion of the rat FEP but did produce an increase in amplitude of the N2P3 component. The data show that the secondary response is not generated by SC in rats, but that SC may modulate amplitude of the response.

Hypothermia and chloropent anesthesia differentially affect the flash evoked potentials of hooded rats.

Anesthetics and body temperature alterations are both known to alter parameters of sensory-evoked responses. However few studies have quantitatively assessed the contributions of hypothermia to anesthetic-induced changes. Two experiments were performed. In the first, chronically implanted rats were injected with either 0, 0.05, 0.10 or 0.20 ml Chloropent/100 g b.w., while body temperature was maintained. Flash evoked potentials recorded 30 min later showed increased latencies but only minor (not statistically significant) changes in amplitude. In the second experiment the same rats were anesthetized with 0.35 ml Chloropent/100 g b.w. and rectal temperature was systematically varied between 31 degrees C and 37 degrees C. Over the ranges of temperature and anesthetic employed, latencies increased more extensively with hypothermia than with anesthesia. P1N1 amplitude doubled when temperature was lowered to 31C, but P2N2 and N2P3 amplitudes declined over the same temperature range. Anesthetic-induced changes in peak-to-peak amplitude did not reach statistical significance when body temperature was constant. The findings suggest that previously reported alterations in evoked potentials following anesthesia may have been confounded with hypothermia.

Pattern reversal visual evoked potentials in awake rats.

A method for recording pattern reversal evoked potentials (PREPs) from awake restrained rats has been developed. The procedure of Onofrj et al. [26] was modified to eliminate the need for anesthetic, thereby avoiding possible interactions of the anesthetic with other manipulations of interest. Rats were restrained in a harness and placed in front of a pattern generating TV screen displaying a black and white alternating square wave grating. Using various stimulation and recording parameters, normative data are presented from 141 adult male Long-Evans hooded and 11 adult male Sprague-Dawley albino rats. Reliable waveforms were recorded with five identifiable peaks. The labels and mean latencies of these peaks in hooded rats were: N1, 47.3 msec; P1, 65.7 msec; N2, 83.3 msec; P2, 94.4 msec; and N3, 129.8 msec. Spatial acuity functions generated with PREPs gave acuity estimates which corresponded closely to values determined behaviorally for hooded and albino rats [4,11].

Surface distribution of flash-evoked and pattern reversal-evoked potentials in hooded rats.

Simultaneous recording from 21 electrode sites in a 4 X 4 mm area over the posterior cortex was used to determine the surface distribution of all major peaks which constitute flash-evoked potentials (FEPs) and pattern reversal evoked-potentials (PREPs) in hooded rats. Topographical maps were constructed with respect to Bregma and midline reference points. The data indicate that not all of the peaks which constitute either evoked potential have their greatest amplitude within the classically defined primary visual cortex. Further, since the FEPs were produced by uniform stimulation, the data suggest that surface regions of the rat visual cortex differ in ways other than simply the portion of the visual field from which information is received.

Depressed excitability and integrated EEGs following hippocampal afterdischarges.

Rats with chronic hippocampal electrode implants had afterdischarges induced with electrical stimulus intensities of 115, 200, and 800% of a previously determined threshold. Afterdischarge duration, postictal EEG depression duration, and the duration of postictal electrical hypoexcitability were assessed. After discharge duration varied inversely with stimulus intensity as did the duration of postictal hypoexcitability. However, the duration of postictal EEG depression increased with stimulus intensity. This dissociation between postictal neuroexcitability and EEG depression is discussed in terms of possible underlying cholinergic mechanisms.

Neonatal triethyltin exposure alters adult electrophysiology in rats.

In adults, triethyltin (TET) produces degeneration of white matter, edema, vacuolization on myelin and histotoxic hypoxia. To determine the functional consequences of perinatal exposure to TET, albino rats were administered either 0, 3, 6, or 9 mg/kg TET on postnatal day 5. Upon reaching adulthood, the rats were implanted with electrodes for recording visual evoked potentials (VEPs) and hippocampal afterdischarges (ADs). In addition to these tests, 17 days of kindling trials were administered to the rats followed by testing with pentylenetetrazol and picrotoxin for seizure susceptibility. TET increased latencies of P2, P3, and N3 of the VEP in a dose dependent fashion. TET also decreases N1P2 amplitudes and produced gender-specific alterations in both P1, N1, and N2 latencies and N2P3 amplitudes. TET produced alterations in duration of the AD recorded from cortex during kindling, but did not produce significant alterations in any of the other variables tested. The results support previous studies, since they show that the adult VEP is sensitive to perinatal toxicant exposure.

Activity changes in rats following acute trimethyltin exposure.

The aliphatic organo-metal derivative, trimethyltin, causes marked morphological damage to the central nervous system (CNS), when the compound is administered by the intragastric route. This report describes certain behavioral consequences of [CH3]3Sn treatment. Either 7.0 mg/kg [CH3]3SnCl or 0.9% saline was injected intragastrically in male rats of Long-Evans strain divided into two equal groups of nine each. Forty days later open-field activity during a 2-min interval was measured for each rat. Following activity testing, the animals were trained to press a lever for food reinforcement on an ascending fixed-ratio series ranging from FR 2 to FR 99. The results showed that rats treated with [CH3]3SnCl were three times as active as controls in the open field, and emitted lever responses at a significantly higher rate than controls throughout the fixed-ratio series regardless of the reinforcement schedule. The possible neuropathological consequences and the relative permanence of the neurobehavioral changes following tin treatment are discussed.

Peak N160 of rat flash evoked potential: does it reflect habituation or sensitization?

Flash evoked potentials recorded from awake rats contain a negative peak occurring about 160 msec after the flash (N160). This peak has been associated with a specific level of arousal, and/or habituation by various authors. The current studies attempted to determine whether changes in N160 amplitude which accompany repeated testing reflect processes associated with sensitization or habituation. This paper describes experiments in Long-Evans hooded rats which demonstrate the effects of repeated testing, varying stimulus intensity, varying stimulus frequency, and discharging an alarm bell before and during a test session. Repeated testing produced increases in N160 amplitude which were greater at high than low stimulus intensities. Repeated exposure to the test chamber without flashing did not alter N160 amplitude, nor did altering stimulus rate within the range of 0.5 to 4.0 Hz. Discharging an alarm increased N160 amplitude. Taken together, the data suggest that amplitude of N160 more closely reflects sensitization to the stimulus than habituation to either the stimulus or any feature of the test situation.

Urethane affects the rat visual system at subanesthetic doses.

Urethane is an anesthetic which is commonly used in neurophysiological studies because it is presumed to have minimal effects upon neuronal activity. This study investigated the influence of urethane anesthesia upon flash evoked potentials (FEPs) recorded from hooded rats. Subanesthetic dosages (25 g/kg and 0.5 g/kg) and an anesthetic dosage (1.0 g/kg) were administered, and subsequently recorded FEPs were compared to vehicle-injected controls. Urethane produced profound qualitative and quantitative effects upon the FEP. At 0.5 g/kg, the P1 (normal latency = 20 msec) and N1 (normal latency = 30 msec) peaks became unrecognizable. Peak N1 disappeared and peak P1 merged with P2 (normal latency = 45 msec). Peak P2 increased in amplitude by about 100%. The results indicate that in the visual system, urethane has a significant influence upon neuronal activity. Caution should be used in interpreting data obtained from urethane-anesthetized rats.

Effects of enucleation in retinal degenerate mice.

Two experiments are reported which examine the effects of optic enucleation upon behavior of retinal degenerate C3H/HeJ mice. Enucleation did not affect acquisition of a two-way avoidance task. However, enucleated mice were more active than unoperated controls. The increased activity was not specific to the avoidance task since it also occurred in the closed field. The enucleation-induced increase in closed field activity did not depend upon age at time of testing or postsurgical recovery time. Several alternative explanations are considered, including the possibility that some information may be processed by the eye in the absence of traditionally conceived photoreceptors.

Rat flash-evoked potential peak N160 amplitude: modulation by relative flash intensity.

The flash-evoked potential (FEP) of rats has a large negative peak (N160) approximately 160 ms following stimulation. This peak has been reported to be modulated by the subject's state of behavioral arousal and influenced by several test parameters. These experiments examined the influences of repeated testing, the number of stimuli/session, interactions of ambient illumination and flash intensity, and the effect of pupillary dilation on the development and amplitude of peak N160. The amplitude of peak N160 increased with daily testing and reached an asymptotic amplitude by about day 10. This amplitude was affected by the intensity of the flash stimulus relative to the ambient illumination (RFI) and appeared to reach a "ceiling" amplitude at greater than 50 dB RFI. The number of stimuli/session and dilation of the subject's pupils did not have a large influence on the growth or asymptotic level of peak N160 amplitude. The data are consistent with the hypothesis that the growth of peak N160 may represent a sensitization-like phenomenon.

Influence of enucleation upon two-way avoidance behavior of rats, hamsters, chinchillas and BALB/cJ mice.

Several rodent species were blinded and their two-way avoidance behavior was compared to unoperated controls. Blindness facilitated avoidance learning in BALB/cJ mice, impaired learning in hamsters and had no significant effect on albino rats, hooded rats and chinchillas. Effects of blindness upon intertrial locomotor activity correlated well with effects of blindness upon avoidance learning. Preventing intertrial activity abolished the effect of blindness in mice, and did not change performance of blind albino rats.

Within-session changes in peak N160 amplitude of flash evoked potentials in rats.

The negative peak occurring approximately 160 ms after stimulation (peak N160) of flash evoked potentials (FEPs) of rats changes with repeated testing. Habituation, sensitization, and arousal have all been invoked to explain these changes, but few studies have directly tested these explanations. We examined within-session changes in peak N160 amplitude with repeated testing, and the modulatory effects of stimulus intensity and auditory white noise. Peak N160 amplitude increased with daily testing (between-session changes), and was larger at greater stimulus intensities. In contrast, peak N160 amplitude underwent within-session increases on early days and within-session decreases on later days. The within-session changes were not affected by stimulus intensity. In rats previously tested in a quiet environment, exposure to acoustic white noise increased motor activity and transiently decreased peak N160 amplitude, which then increased and subsequently decreased with continued photic and acoustic stimulation. Repeated testing in the presence of noise did not alter the within-session changes in peak N160 amplitude. Heart rate showed both within- and between-session decreases, but was unaffected by noise. The data suggest that the within-session changes in peak N160 amplitude may reflect a habituation-like response to the test environment.