Tyrosine ameliorates a cold-induced delayed matching-to-sample performance decrement in rats.

Exposure to cold stress has been shown to impair short-term, or working, memory which may be related to a reduction in brain catecholamines. Administration of the catecholamine precursor tyrosine may alleviate a cold-stress-induced memory impairment by preventing a deficit in brain catecholamine levels. To test this hypothesis, eight rats performed a delayed matching-to-sample (DMTS) task at an ambient temperature of either 2 degrees C (cold) or 22 degrees C, following intraperitoneal administration of saline or tyrosine (50, 100 or 200 mg/kg). Rats administered saline prior to 22 degrees C exposure demonstrated a characteristic delay gradient in which accuracy decreased as the delay interval between sample and comparison stimuli increased from 1 to 16 s. Consistent with previous research, and relative to 22 degrees C exposure sessions, matching accuracy during 2 degrees C exposure sessions was reduced, which is attributed to the effect of cold on short-term, or working, memory. In particular, during cold exposure sessions matching accuracy was significantly reduced at the longer delay intervals, relative to matching accuracy at 22 degrees C. Additional analysis of cumulative matching errors within sessions showed that during exposure to cold, errors occurred at a constant rate throughout the session, indicating rats' performance was equally debilitated by the stressor over the entire session. During cold exposure sessions, the higher doses of 100 and 200 mg/kg tyrosine significantly improved overall matching accuracy relative to saline, but did not completely reverse the effect of cold exposure, as overall matching accuracy did not increase entirely to levels obtained at 22 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic responses to cognitive activity in a cold environment.

Adrenergic responses during physical stress such as cold exposure have been reported to differ from those responses observed during cognitive activity. Both the separate and the combined effects of cold and cognitive activity on catecholamine activity were examined in six male subjects. Alterations in plasma epinephrine and norepinephrine showed different patterns as a function of exposure to a 4 degrees C cold environment, a cognitive performance assessment battery (PAB), and the two conditions combined. Plasma epinephrine was not altered by exposure to cold and only slightly increased by PAB performance when given at 23 degrees C. However, epinephrine was substantially elevated by exposure to combined cold and PAB. Heart rate changes paralleled observed changes in epinephrine. Norepinephrine release was predominantly increased by cold exposure and was not altered by PAB performance.

Alteration of response patterning by d-amphetamine on repeated acquisition in rats.

The acute effects of d-amphetamine on response patterning in a repeated acquisition baseline were investigated with rats. Each session the animals acquired a different four-member response sequence on three levers. Each sequence (trial) completion produced a food pellet. Errors produced a brief timeout that was reset by responses made during the timeout. Acute doses of d-amphetamine (0.5-4.0 mg/kg) and saline were administered 30 min presession. The response patterns analyzed were perseverative responses to a single lever (runs), and a response to each lever in either a left-to-right or right-to-left direction (traverses). The trial position, frequency, and lever location of error and timeout responses that occurred in the context of runs and traverses were studied. In contrast to control sessions, higher doses of d-amphetamine produced increases in the number of error and timeout responses emitted. The majority of these responses occurred as runs; traverse responding did not exceed control levels. Furthermore, the run error and timeout responding tended to occur early in the session and on a single response lever. The results are consistent with the view that d-amphetamine disrupts stimulus control and produces perseverative responding which may account for previous reports of disruption in repeated acquisition tasks following d-amphetamine administration.

Tyrosine reverses a cold-induced working memory deficit in humans.

Acute exposure to cold stress has been shown to impair short-term, or working, memory, which may be related to reduction in, or disruption of, sustained release of brain catecholamines. Administering a supplemental dose of the catecholamine precursor tyrosine may alleviate cold stress-induced memory impairments by preventing cold-induced deficits in brain catecholamine levels. The present experiment determined whether administration of tyrosine would prevent a cold-induced working memory deficit, using a computer-based delayed matching-to-sample (DMTS) memory task. Eight male volunteers performed the DMTS task for 30 min at an ambient temperature of either 4 degrees C (cold) or 22 degrees C following a 30-min preexposure period and 2 h after ingesting 150 mg/kg of L-tyrosine or placebo. Subjects demonstrated a decline in matching accuracy on the DMTS task as delay interval increased, such that matching accuracy following a 16-s delay between sample and comparison stimuli was lower than that following a delay of 2 or 8 s. Consistent with previous research, and relative to 22 degrees C exposure sessions, matching accuracy during 4 degrees C exposure sessions was reduced significantly following placebo administration, which is attributed to the effect of cold exposure on short-term, or working, memory. Administration of tyrosine significantly improved matching accuracy at the longest delay interval most affected by cold exposure, such that matching accuracy in the cold following tyrosine was at the same level as matching accuracy following placebo or tyrosine administration at 22 degrees C. Tyrosine administered prior to 22 degrees C exposure had no effect on DMTS performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of d-amphetamine and cocaine on repeated acquisition with timeout from avoidance.

The acute effects of d-amphetamine and cocaine on a repeated acquisition baseline with timeout from avoidance were investigated in two rats. Each session the animals acquired one of two different three-member response sequences. Each sequence member was associated with a different response lever. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout (30 sec) from avoidance. Incorrect responses did not postpone shock. The baseline performance was characterized by a decrease in errors within each session, similar to patterns of repeated acquisition maintained by food. In comparison to control sessions, both d-amphetamine and cocaine increased errors and altered the pattern of within-session acquisition. d-Amphetamine increased the rate of sequence completion and the rate of shock delivery in both animals. Cocaine increased the rate of sequence completion in one animal and increased the rate of shock delivery for the other.

A yoked-chamber comparison of concurrent and multiple schedules: the relationship between component duration and responding.

Two experimental chambers were electrically connected so that the component selected by a pigeon confronting concurrent variable-interval schedules in one chamber could be successively presented as a multiple schedule to a second pigeon in the other chamber. Component duration was regulated by the use of a changeover delay, the value of which was systematically varied between 0 and 30 sec. It was found that the relative local response rates on the preferred key (absolute response rate to that component divided by the sum of the absolute response rates during both components) tended to increase with increasing component durations for the birds in the concurrent chamber, but decreased for the birds in the multiple chamber. These data support the interpretation that there are fundamental differences in the mode of responding to multiple and concurrent schedules. Based on these findings, it was concluded that previous demonstrations of matching on multiple schedules do not establish that response allocation is controlled by a process equivalent to that found on choice paradigms. It now appears that matching on multiple (but not concurrent) schedules is a consequence of selecting short component durations. The implications of these data for Herrnstein's (1970) and Rachlin's (1973) formulations of the relationship between multiple and concurrent schedules are examined.

Repeated acquisition of conditional discriminations.

A new technique was developed to study the repeated acquisition of conditional discriminations. Using a discrete trial procedure, pigeons were required to learn during each session a different two-member chain of conditional discriminations. Key color and geometric forms were used as stimuli. After the pigeons had reached a steady state of relearning (40 to 60 sessions), the technique was used to investigate variables that have previously been shown to affect the repeated acquisition of response sequences. Various (0 to 90 seconds) durations of timeout for errors were investigated in Experiment I. The stimulus change associated with a timeout, rather than its duration, was found to be the critical variable in acquisition of the discrimination. Extended training on a single chain was found to reduce total errors across sessions in Experiment II. Extended training (three sessions) did not, however, change the pattern of within-session error reduction. In some cases, extended training facilitated acquisition of a partially reversed discrimination. In Experiment III, color rather than chain position was found to control behavior, for three of the four birds, as the second stimulus dimension in the conditional situation. The results of these experiments replicate and extend previous findings concerning some of the variables that affect the repeated acquisition of response sequences.

Sequential reacquisition as a function of timeout from avoidance.

Rats learned to reacquire four similar three-member response sequences. Each sequence member was associated with a different response lever, and the correct sequence of levers (i.e., 3-1-2, 2-1-3, 1-3-2, and 2-3-1) changed each session. The first two correct responses of each sequence postponed shock for a fixed period of time. The third correct response initiated a signalled timeout from avoidance. Incorrect responses did not affect the shock interval or reset the sequence. The effects of manipulating timeout duration on the sequential reacquisition baseline were investigated. All subjects displayed biphasic reacquisition performances similar to those controlled by food. The phases were characterized by an initial increase in accuracy, which reached a stable level during the latter portion of each session. Timeout duration affected rate of sequence completion and shock density, but not percentage of errors. Rate of sequence completion was fastest with intermediate timeouts (15 to 60 sec), and slowest with extreme durations (1 or 120 sec). Shock densities peaked with extreme durations and were at minimum with intermediate timeout values. The percentage of errors was the same across timeout durations. These data extend the generality of sequential reacquisition as a procedure for studying learning, and demonstrate timeout from avoidance to be a controlling variable.

Effects of cocaine and d-amphetamine on the repeated acquisition and performance of conditional discriminations.

The acute and chronic effects of cocaine and d-amphetamine on food-reinforced behavior were investigated in pigeons responding on a two-component multiple schedule. In one component, the behavioral task consisted of the same chain of conditional discriminations each session (performance). In the other component, the chain of conditional discriminations was changed from session to session (learning). In comparison to control sessions, both acute cocaine and d-amphetamine increased errors in each component of the multiple schedule. Responding in the learning component, however, was generally disrupted at lower doses than those that affected responding in the performance component. At high doses, both drugs produced pauses in responding in each component in three of the four subjects. Pausing engendered by d-amphetamine was approximately twice as long as that under cocaine. Upon chronic administration, both the pausing and error-increasing effects of each drug diminished. Drug-induced changes in timeout responding, however, did not decrease during chronic administration. Redeterminations of the d-amphetamine dose-effect curves following chronic cocaine administration suggested the existence of cross-tolerance between cocaine and d-amphetamine. Both the acute and chronic data are consistent with the view that conditions of stimulus control may modulate the behavioral effects of drugs.

Repeated exposure to moderate cold impairs matching-to-sample performance.

To study effects of moderate cold (5 degrees C) on complex cognitive performance, subjects were exposed to cold while responding on a conditional discrimination task. The task required a correct choice of which of two simultaneously presented matrices matched a previously presented sample matrix. The effects of task performance in cold and ambient temperatures was examined on three repeated occasions, one pair of conditions per week. Responses accuracy was consistently impaired in each cold session. In addition, choice response latencies lengthened and sample response latencies decreased in all cold exposures. The data show that even moderate cold exposure that does not produce core hypothermia can impair performance of a complex cognitive task and that the magnitude of performance change is not attenuated by a brief series of cold exposures.

Moderate cold exposure shortens evoked potential latencies in humans.

Visual, auditory event-related potentials, and brainstem auditory-evoked responses were recorded in as many as six young male subjects in order to study the effects of moderate cold air exposure on central nervous system functioning. Evoked potentials were recorded during repeated 50-min exposures to air of 4 and 22 degrees C; these levels of exposure resulted in no change in rectal core temperature. Evoked potentials recorded during exposures to 4 degrees air displayed consistently shorter latencies compared to those recorded at 22 degrees, suggesting faster CNS processing of sensory stimuli in the cold. These results are consistent with recent investigations of cold-induced behavioral response changes which indicate that increased arousal may occur with moderate (nonhypothermic) cold exposure.

Multiple schedule performance changes during carbon monoxide exposure.

Behavioral effects of carbon monoxide (CO) were studied in rats during 90 min exposures to concentrations ranging from 250 to 850 parts-per-million (PPM). The animals performed on a multiple fixed-ratio differential-reinforcement-of-low-rate (MULT FR 30 DRL 18) schedule of food reinforcement. Periodically, the animals were individually exposed to either air or CO for 30 min periods prior to as well as during 60 min test sessions. Carboxyhemoglobin measurements indicated equilibration after 60 min of exposure. Concentrations of 650 PPM or higher produced response rate reductions. The decreased response rates were due primarily to abrupt cessation of responding during CO exposures. Response patterning in both FR and DRL components remained intact until responding ceased. The accuracy of responding in the DRL component as measured by the distribution of inter-response-time (IRT) intervals was not systematically affected by CO exposure.

Cold-induced impairment of delayed matching in rats.

Exposure to moderate, nonhypothermic cold temperature has been reported to affect a variety of behavioral and neural functions. To elucidate the effects of mild cold stress on short-term (working) memory, Long-Evans rats were exposed to an ambient temperature of either 2 degrees or 23 degrees C while performing a delayed matching task. At the beginning of each trial, rats were required to respond on one of two levers cued by a light. Following a delay of 2, 8, or 16 s, a response on the lever previously cued produced food reinforcement. Relative to performance at 23 degrees C, exposure to 2 degrees C occasioned no change in matching accuracy at the 2-s delay, a modest decrement at the 8-s delay, and a larger decrement at the 16-s delay. The cold exposure did not decrease colonic temperature. In addition to accuracy decrements, matching response times were consistently shorter during cold exposures. Cold-induced impairments were absent during removal of the memory component from the task, indicating the observed cold effects on memory were not due to impaired attentional, sensory, or motor processes. These data suggest that mild cold stress may impair active maintenance of information in working memory but not processes related to reference memory.

Low-intensity magnetic fields alter operant behavior in rats.

The present study demonstrates that operant behavior is affected by a combination of a 60-Hz magnetic field and a magnetostatic field 2.6 X 10(-5) T (about half the geomagnetic field). Rats exposed to this combination for 30 min consistently exhibited changes in the rate and pattern of responding during the differential reinforcement of low rate (DRL) component of a multiple fixed ratio (FR) DRL reinforcement schedule. By contrast, there were no measurable changes following exposure to the static field alone or to the oscillating field alone, even with a 10-fold increase in intensity (5 X 10(-5) to 5 X 10(-4) Trms). A cyclotron resonance mechanism has been suggested as a possible explanation for the observation that weak static magnetic fields modify the response of in vitro brain tissue to low-frequency magnetic fields. The choice of static field intensity Bo and frequency nu in the present study follows from the cyclotron resonance condition nu = (1/2 pi)(q/m)Bo, for singly charged lithium, an element in extensive use in the clinical treatment of affective disorders in humans. The present research is consistent with a cellular cyclotron resonance mechanism and tends to imply a functional dependence of behavior on the geomagnetic field.

Intensity threshold for 60-Hz magnetically induced behavioral changes in rats.

Experiments were conducted to further investigate the effect of 60-Hz cyclotron-resonance exposures on rats performing on a multiple FR-DRL schedule. The previously reported temporary loss of DRL baseline response, when measured as a function of A.C. magnetic intensity, was found to have a threshold. Utilizing the component of A.C. magnetic intensity parallel to the D.C. field, we report this threshold as (0.27 +/- 0.10) x 10(-4) Trms.

Modification of the repeated acquisition of response sequences in rats by low-level microwave exposure.

The acute effects of microwave exposure on a repeated acquisition baseline were investigated in three rats. Each session the animals acquired a different four-member response sequence. Each of the first three correct responses advanced the sequence to the next member, and the fourth correct response produced food reinforcement. Incorrect responses produced a three-second timeout. Baseline and control sessions were characterized by a decrease in errors within each session. The animals were acutely exposed to a 2.8 GHz pulsed-microwave field prior to test sessions, with average power densities ranging from 0.25 to to 10 mW/cm2. In comparison to control sessions, 1/2 hour of exposure to microwave radiation at power densities of 5 and 10 mW/cm2 increased errors and altered the pattern of within-session acquisition. Exposure to the 10 mW/cm2 power density decreased the rate of sequence completion in all animals. The results of exposures at 0.25, 0.5, and 1 mW/cm2 power densities were generally within the control range. The results are interpreted as indicating a disruption in the discriminative stimulus control of the repeated acquisition behavior.

Behavioral effects of chlorpromazine and diazepam combined with low-level microwaves.

Previous research findings on the interaction between drugs and microwave radiation were extended to chlorpromazine and to diazepam. The drugs were combined with a 1 mW/cm2 pulsed microwave field (2.8 GHz) and effects were measured on a fixed interval (FI 1) schedule of food reinforcement with rats. Dose-effect functions with and without sham irradiation were established for each drug. At effective doses chlorpromazine consistently decreased rate of responding and reduced with-interval response patterning. Low to moderate doses of diazepam produced little change or increases in response rate, and higher doses produced a decline in response rate. Response patterning within intervals was reduced by increasing doses of diazepam. The animals were exposed to the microwave field alone before test sessions combining the drugs with microwave radiation. Microwave exposure alone did not affect FI performance. Microwave radiation in combination with either drug did not produce any alterations in the dose-effect functions.

Temporal changes in repeated acquisition behavior after carbon monoxide exposure.

Behavioral effects of carbon monoxide (CO) were studied in rats following 90-min exposures to concentrations ranging from 500 to 1200 parts-per-million (ppm). The animals performed on a repeated acquisition of behavioral chains procedure in which food reinforcement depended on the correct completion of a four member response sequence on three separate response levers. The sequence of correct lever presses changed daily. Periodically, the animals were individually exposed to either air or a CO concentration of 500, 850, or 1200 ppm for 90 min prior to a behavioral session that terminated after the completion of 150 sequences. Carboxyhemoglobin measurements indicated equilibration after 60 minutes of exposure. Concentrations of 850 and 1200 ppm produced increased pausing between responses throughout the test sessions. The increased time required to complete sequences occurred primarily during the first component of the response sequence. Accuracy of responding as measured by total error and timeout responses was not affected by CO exposure.

Comparative effects of pulsed and continuous-wave 2.8-GHz microwaves on temporally defined behavior.

The effects of pulsed-(PW) and continuous-wave (CW) 2.8-GHz microwaves were compared on the performance of rodents maintained by a temporally defined schedule of positive reinforcement. The schedule involved food-pellet reinforcement of behavior according to a differential-reinforcement-of-low-rate (DRL) contingency. The rats were independently exposed to PW and to CW fields at power densities ranging from 1 to 15 mW/cm2. Alterations of normal performance were more pronounced after a 30-minute exposure to the PW field than to the CW field. The rate of emission of appropriately timed responses declined after exposure to PW at 10 and 15 mW/cm2, whereas exposure at the same power levels to the CW field did not consistently affect the rate of responding. Change in performance associated with microwave exposure was not necessarily related to a general decline in responding; in some instances, increases in overall rates of responding were observed.