Wintersweet (Chimonanthus praecox) toxicity in four goats.

CASE HISTORY: A one-year-old female goat presented with acute onset of recumbency, seizures and vocalisation approximately 5 hours after being given access to branch trimmings from a neighbour's garden. The plant from which the pruned branches came was subsequently identified as wintersweet (Chimonanthus praecox). Three other goats kept in the same paddock displayed similar clinical signs over a period of 4 hours following the initial presentation. CLINICAL FINDINGS: All four goats were ataxic, displayed tetanic seizures and were in lateral recumbency; they had dilated pupils and were hyperaesthetic, with elevated heart and respiratory rates. After symptomatic treatment, including sedation with diazepam, one of the three goats continued to deteriorate and was subjected to euthanasia. The remaining three goats recovered over 1-14 days with nursing care and physiotherapy. DIAGNOSIS: Toxicity due to ingestion of wintersweet, which contains the alkaloid calycanthine. CLINICAL RELEVANCE: Calycanthine is a central nervous system toxin, causing convulsions. Wintersweet shrubs are present in many New Zealand gardens. Practitioners should be aware that the seeds and flowers, and possibly the leaves, of this plant are highly toxic with signs of toxicity including ataxia, hyperaesthesia and seizures.

Effects of medial septal lesions on an operant go/no-go delayed response alternation task in rats.

Previous work in our laboratory has found that whereas medial septal lesions impaired an operant left-right delayed alternation task in rats, the lesion also facilitated the performance of rats on a cued go/no-go discrimination task with a delay between the cue and the required response. These findings suggested to us that the medial septal lesions impaired "response" working memory, which in turn led to a compensatory enhancement of attention to stimulus cues. If this hypothesis is true, then the lesions should impair a go/no-go task based on "response" working memory. The current experiment tested this hypothesis. Rats (12 with medial septal lesions and 12 with sham operations) were tested on a discrete trial operant go/no-go response alternation task. The rats were first tested for 20 days without a delay contingency, followed by 35 days of testing with a 15-s delay between "go" and "no-go" trials. Both groups became proficient at the task under nondelay conditions and their terminal performance (averaging about 85% correct) did not differ. However, under delay conditions the performance of the lesioned rats was significantly impaired compared to the controls. As the go/no-go task does not require a spatial discrimination, the best explanation for our findings is that the lesions impaired response working memory.

Effects of medial septal lesions on an operant delayed go/no-go discrimination in rats.

Male hooded rats received either a medial septal lesion or a control operation. The rats were then tested on an operant go/no-go discrimination task, first without a delay contingency (20 days), followed by 25 days under an 8-s delay. A discrete trial procedure with symmetrical reinforcement was used. Each trial began with the operant chamber darkened, except for back illumination of a centrally located press panel. Depression of this panel extinguished the back light and initiated a random presentation of either the go stimulus (2800 Hz tone) or the no-go stimulus (10 Hz pulsing light) for 3 s. Stimulus termination initiated the appropriate delay contingency (0 s or 8 s), which was followed by the cued availability of a lever for 2 s. If the rat pressed the lever on go trials, or refrained from pressing the lever on no-go trials, a food pellet was delivered. The data (% correct responses) were averaged over 5-day blocks. Overall, the septal-lesioned rats performed significantly better than the control rats under both O-s delay (p < 0.025) and 8-s delay (p < 0.001) contingencies. Although there was not a significant difference between the groups during the last block of the O-s delay (septals 93% correct, controls 89% correct, p > 0.05) or the first block of the 8-s delay (septals 54% correct, controls 53% correct, p > 0.05), the septal-lesioned animals performed significantly better than the controls during all the remaining phases of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Medial septal lesions impair performance on a preoperatively acquired delayed alternation task.

Male hooded rats were preoperatively trained to perform an operant delayed alternation (DA) task. The rats were tested, for 10 days each, on DA at 5-, 10-, 20-, and 30-s delays. The rats were then randomly assigned to serve as control subjects or receive a medial septal lesion. Following surgical recovery the rats were retested on DA in the exact manner as they were tested preoperatively. Prior to surgery the groups did not differ, but all rats improved over days of testing, and performed better at short delays than at long delays. In contrast, group differences were obvious following surgery, with the septal-lesioned subjects showing a clear impairment. The control subjects ranged between 85% correct (end of 5-s delay) to 65% correct (end of 30-s delay), while the septal-lesioned rats ranged between 72% correct (end of 5-s delay) to 50% correct (end of 30-s delay). The results are discussed in terms of a working memory impairment produced by the septal lesions.

Effects of medial septal lesions on operant delayed alternation in rats.

The septohippocampal system regulates spatial behavior, memory and response flexibility. This experiment determined which of these functions is disrupted by medial septal lesions which impair operant delayed alternation in rats. Male hooded rats received either medial septal lesions or a control operation. Following recovery, they were reinforced for alternating left and right lever presses in an operant chamber. The effects of various delays (0, 10 and 20 s), and exteroceptive cues were assessed. Medial septal lesions did not impair alternation performance at the 0-s delay, but did produce severe impairments at the 10- and 20-s delays. An exteroceptive light cue which reduced the spatial requirements of the task did not ameliorate this impairment. However, an exteroceptive light cue which reduced the working-memory requirements of the task did ameliorate the lesion-induced deficit on delayed alternation. While the lesioned rats also made more perseverative errors than the controls, statistically removing this influence from the data did not modify the results. These data suggest that medial septal lesions in rats impair operant delayed alternation by disrupting the general process of working-memory rather than spatial behavior or response flexibility.

Effects of Pavlovian conditioning on the ethanol withdrawal syndrome in rats.

Male, hooded rats were made physically dependent upon ethanol using intravenous infusions. Following this induction procedure, physical dependence was maintained, but now a tone (CS) was associated with ethanol infusions (US) that reduced withdrawal distress. A pretest-posttest, counterbalanced, repeated measures design was used to assess the effects of three treatments (ethanol, tone, none) on withdrawal reactions (withdrawal signs, body temperature, open-field activity) measured under blind conditions. Only the ethanol treatment reduced withdrawal distress, suggesting that classical conditioning did not occur. The results are discussed in terms of recent conditioning theories of drug responses, and the potential role of stress in these reactions.

Absence of reinforcement with low dose intravenous ethanol self-administration in rats.

Male hooded rats were implanted with intravenous cannulas and housed in operant chambers supplied with 2 levers and enclosed in sound-attenuating cubicles. In Experiment 1, seven rats received a 1.0 mg/kg infusion of ethanol for each press on the previously determined non-preferred lever. The other lever served to count "activity lever presses." An additional 7 rats served as controls and were treated identically except that each press on the non-preferred lever led to an infusion of saline, isovolumetric to the ethanol infused in the experimental subjects. The rats were tested under these conditions of continuous reinforcement for 9 days. Throughout this period, self-infusions and "activity lever presses" did not differ between the groups, suggesting that ethanol was not reinforcing at a dose of 1.0 mg/kg. These results were replicated, and extended to other low doses of ethanol in Experiment 2. Here, we employed a design where depression of either lever, under conditions of continuous reinforcement, led to the infusion of a solution. Fifteen rats were randomly assigned to one of three groups (5 rats/group). In one group, depression of the previously determined non-preferred lever led to an infusion of 16.0 mg/kg of ethanol, while depression of the other lever led to an infusion of isocaloric glucose. For the other two groups, depression of the non-preferred level led to an infusion of 4.0 and 1.0 mg/kg ethanol respectively, and depression of the other lever led to a glucose infusion. The animals were tested for 9 days, and in each case, ethanol self-infusions did not differ significantly from glucose self-infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of two intravenous infusion schedules for inducing physical dependence upon ethanol in rat.

Male hooded rats were implanted with intravenous (IV) cannulas and housed in operant chambers. The effectiveness of two infusion schedules for producing physical dependence upon ethanol was assessed. Twenty-three rats (12 ethanol, 11 control) were tested under a 4 hr interinfusion schedule (one infusion every 4 hr, around the clock), and 29 rats (15 ethanol, 14 control) were tested under a 2 hr interinfusion schedule. During the dependence induction phase, which lasted for 6 days, the experimental rats received ethanol (30% v/v) at an average daily dose which ranged from 8.4-11.8 g/kg, and the dose administered per infusion was adjusted according to the degree of intoxication of each animal. The pair-fed control subjects received infusions of isocaloric control solutions (either 29% v/v propylene glycol or 31% v/v glycerol). Following the dependence induction phase, ethanol was withdrawn, and withdrawal symptoms were assessed. Blood ethanol levels (BEL) and signs of intoxication were determined through all phases of the experiment. During the dependence induction phase, mortality was close to zero, and weight loss was held to about 10%. Tolerance to ethanol developed in all experimental rats. During the withdrawal period, all ethanol rats developed clear withdrawal symptoms, while control subjects did not. Ethanol elimination rates ranged between 45-50 mg/dl/hr and withdrawal symptoms began when BEL fell below 200 mg/dl, and were severe when BEL approached zero. The 2 hr schedule proved superior to the 4 hr schedule in that it led to greater stability of BEL during dependence induction, and a tendency for the withdrawal reaction to be more severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Septal lesions and active avoidance performance in rats: effects of differential intrabox cues.

In two separate experiments, male rats received septal lesions and were compared to operated controls on the acquisition of a two-way active avoidance task. In both experiments, an automated active avoidance apparatus (Lafayette Instrument Co.) was used, and the animals were tested 10 trials each day, 6 days/week. The CS was a tone, and the US was a 0.7 mA shock; the CS-US interval was 7 seconds. In Experiment 1, the rats (N = 6/group) were tested under conventional conditions. The two compartments of the avoidance apparatus were identical in all respects. In Experiment 2, the rats (N = 6/group) were tested in the same apparatus, but with differential intrabox cues. The inside of the left compartment was lined with black contact paper, while the inside of the right compartment was lined with white contact paper. Irrespective of the conditions, the septal rats were facilitated in the acquisition of shuttle-avoidance. In both tasks, the septal subjects required fewer trials to reach criterion, and showed better orientation in the shuttle-box compared to controls. The response latencies of the septal subjects also tended to be faster, but neither septal nor control subjects showed differential response latencies related to the direction of the shuttle response. Previous findings have shown that the addition of external cues to purported spatial tasks can reduce the behavioral effects produced by damage to the septohippocampal axis on such tasks. The present results suggest that such a cue-addition procedure does not influence the behavioral effects produced by septal lesions in shuttle-avoidance.

Multiple exposures to ethanol facilitate intravenous self-administration of ethanol by rats.

In Experiment 1, male hooded rats (N=11) were implanted with jugular cannulas, and housed in sound attenuated operant chambers 24hr/day. The rats were exposed to periodic cycles of forced ethanol infusions (30% v/v, 9-16 g/kg/day over 4-6 days for each cycle). Following each cycle, forced infusions were discontinued, but the rats were allowed access to lever for self-administration of ethanol on a fixed ration 1 schedule (FR1). Each lever press infused 0.2 ml of ethanol (20% v/v). The rats were maintained on self-administration for at least 24 hr. If a rat did not develop self-administration behavior (SAB) within 24 hr, the next forced cycle fo ethanol exposure was initiated. Eight of the 11 rats developed SAB after a mean of 5.25 cycles of exposure to ethanol, and were then tested for a mean of 15 days on self-administration under FR1, FR2, and FR3 schedules of reinforcement. All rats were tested on FR1 and days of self-administered a mean of 10.43 g ethanol/kg/day over a mean of 10.75 days. Four rats were subsequently tested on FR2 and FR3 and increased lever presses in order to maintain daily ethanol intake comparable to FR1. Following self-administration testing, the rats were placed on withdrawal and exhibited mild to severe withdrawal symptoms, suggesting that SAB maintained physical dependence. In Experiment 2, rats (N=6/group) were allowed to self-infuse either saline or ethanol (20% v/v). These rats had no prior exposure to either saline or ethanol, and forced infusion were never administered. The rats remained in their operant chambers for 21 days under FR1 contingencies. Each lever press led to a 0.2 ml infusion. None of the rats developed SAB, but the saline controls made more lever presses than the ethanol rats (p less than 0.01). These results suggest that the ethanol parameters yielding SAB in Experiment 1 are aversive to ethanol naive rats.

Induction of physical dependence upon ethanol in rats using intravenous infusion.

Intravenous infusions were used to produce physical dependence upon ethanol in rats. The procedure proved to be safe, rapid, and reliable. Ethanol (30% v/v) was administered over a 7-day period. The mean daily dose ranged from 10--14 g/kg/day. Control rats were exposed to a comparable procedure except that saline, rather than ethanol, was infused. All ethanol treated rats that survived the intoxication period (n = 11) showed signs of physical dependence (moderate to severe, n = 8; mild, n = 3) following ethanol withdrawal. Saline treated rats (n = 8) did not show any of these symptoms. The most reliable ethanol withdrawal signs observed were: spontaneous seizure (n = 7), audiogenic seizure (n = 7), tremors (n = 6), tail stiffening (n = 10) and body rigidity (n = 9). These symptoms were analyzed in terms of their hour of onset and hour of maximum intensity following ethanol withdrawal. Application of the intravenous method for the study of ethanol self-administration is discussed.

Secondary reinforcement property of a stimulus paired with morphine administration in the rat.

Rats learned to run to the correct arm of a Y-maze. Correct responses were reinforced with morphine injection paired with a conditional tone stimulus. After the maze response was well established, extinction trials were run. During extinction half of the animals received neither morphine nor tone as a consequence of a correct response, while the other half received the tone but no morphine. Rats receiving the tone during extinction required significantly more trials to reach the extinction criteria than rats not receiving tone presentations. Extinction with the tone also facilitated relearning of the maze response. The results support the view that morphone is a potent reinforcer, and that stimuli paired with morphine administration acquire the properties of a secondary reinforcer.

Alleviation of narcotic withdrawal syndrome by conditional stimuli.

We systematically paired auditory, olfactory, and social stimuli with each injection of morphine in rats. We found that, when morphine was kept constant at a low dose, the external stimuli acquired the property of a conditional stimulus (CS) to cause hyperthermia which was antagonized by naloxone. In rats in which morphine doses were regularly increased to cause morphine dependence, the CS presented during withdrawal, caused reduction in withdrawal signs (wet shakes, hypothermia, aggression) and produced hyperglycemia as well as elevation of striatal homovanillic acid. CS-induced alleviation of withdrawal hypothermia was blocked by mecamylamine, phenoxybenzamine, haloperidol, benztropine or naloxone but not by cyproheptadine or propranolol.

Reduction of morphine-withdrawal body shakes by a conditional stimulus in the rat.

Narcotic dependence in rats was established, in five days, by administering intravenous injections of morphine sulfate in increasing doses. From day six onward, dependence was maintained by administering a morphine injection (15 mg/kg) every 6 h throughout the day, and each of these injections was paired with a tone. After 16 morphine-tone pairings, test trials, in which the tone was presented in the absence of morphine, were instituted. These tone presentations significantly reduced morphine-withdrawal "wet shakes" in rats which received morphine-tone pairings, but not in rats which received control treatments.

Acquistion and extinction of a conditioned hyperthermic response to a tone paired with morphine administration.

Following a 7-day baseline period, five male hooded rats were injected daily with a constant dose (20 mg/kg) of morphine sulfate. Immediately following the injections they were taken to a sound-attenuated room and exposed to a 5,000 cps tone for 90 min. On certain predetermined days of the morphine treatment, rectal temperatures were measured before each injection and 30 min following the onset of the tone. Also, after the 11th, 19th, and 57th morphine-tone pairing, the rectal temperatures were measured before and after a saline injection which was paired with tone. On these days tone presentations by themselves were sufficient to cause a reliable increase in rectal temperature resembling that seen following an injection of morphine. When tone presentations were continued, without further pairing with morphine, the hyperthermic response to the tone was gradually extinguished. However, a significant increase in rectal temperature in response to the tone was again observed following a second set of five morphine-tone pairings.