Comparison of Bricanyl® Turbuhaler and Berotec® dry powder inhaler

Terbutaline (Bricanyl) 0.5 mg t.i.d. administered via Turbuhaler was compared with fenoterol (Berotec) 0.2 mg t.i.d. administered via Inhalator Ingelheim in 36 asthmatic children aged 7-12 years. The study was of an open crossover design with two randomly allocated treatment periods, each lasting 2 weeks. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured at clinic visits before study start and at the end of each treatment period. The patients recorded peak expiratory flow (PEF) before and after inhaler use, morning and evening. They also recorded asthma symptoms and number of extra inhalations. At the end of the study, children and parents were asked for inhaler preference. No differences between the treatments were found concerning the results of the lung function measurements at the clinic or at the PEF measurements at home. No differences were found between the treatments as regards asthma symptoms or number of extra inhalations. Two patients experienced mild side effects during fenoterol treatment, none during terbutaline treatment. Treatment with terbutaline in Turbuhaler was preferred by a majority of children and parents. In conclusion, in this group of asthmatic children, treatment with terbutaline administered via Turbuhaler was as efficacious as treatment with fenoterol administered via Inhalator Ingelheim. There was a clear preference in favour of the Turbuhaler.     

Limb preference after unilateral pyramidotomy in adult and neonatal rats

As previously reported, unilateral pyramidotomy in newborn rats results in the development of an aberrant ipsilateral corticospinal tract that originates from the intact side. In the present study, limb preference after unilateral pyramidotomy in adult and neonatal rats was examined in search of differences that might correlate with this aberrant tract. However, no significant differences were observed between the two groups. Postoperatively, adult animals preferred the limb corresponding to the intact corticospinal tract in spite of a pre- and postoperative testing bias toward the opposite limb. Similarly, the animals that sustained neonatal lesion followed by testing at maturity also preferred the limb corresponding to the normal crossed corticospinal tract.     

Retention of a backward classically conditioned reflex response in spinal cat

Summary Retention of a backward classically conitioned reflex response was investigated in the spinal cat preparation. Facilitation of the flexion reflex was induced by the pairing of superficial peroneal nerve stimulation (30 Hz, 0.5 s), the US (unconditioned stimulus), with saphenous nerve stimulation (10 Hz, 1.5 s), the CS (conditioned stimulus). Both the US and CS were supramaximal for activation of A cutaneous afferent fibers. Experimental animals received 30 paired trials (US preceded CS by 0.25 s) with an intertrial interval (ITI) of three min. Control animals received the same stimuli but in an explicitly unpaired manner. Following acquisition, all animals received 30 additional CS-alone trials at five min intervals. This paradigm, which incorporated ITIs longer than those which had been used previously in backward conditioning studies, induced a long-lasting potentiation of the flexion reflex which appeared to be specific to spinal reflex pathways activated by A cutaneous fibers. The relevancy of these results to a more specific understanding of backward and forward classical conditioning in the spinal cat is discussed.Supported by NSF grants 8415917 and 8808495     

Effect of insulin on sex differences in the intake of glucose solutions in rats

Adult male and female Wistar rats maintained on ad lib diet were given a choice between tap water and a solution of glucose in the concentration of either 5 or 12%. Both sexes exhibited a marked preference for glucose solutions. With the 5% solution the volume intake was similar in both sexes and the total calorie intake was normal. With the 12% solution the volume intake was higher in females than in males, while in both sexes the total calorie intake was increased to a similar (maximum acceptable) level. Treatment with Protamine Zinc Insulin (PZI) in a daily dose of 40 U/kg b.w. markedly increased the intake of the 5% solution in both sexes, but significantly more in females than in males, thus revealing sex differences which were not manifest in untreated rats. PZI treatment had little effect on 12% glucose solution intake, presumably because with this solution the total calorie intake was increased to a maximum already in untreated rats.     

Taste preferences in a free-choice situation following electrical stimulation and lesion of septal area in rats

In the present study, electrical stimulation of medical or laternal septal areas and total or restricted lesions of these were conducted to observe the effect on ingestion of primary taste solutions in a free-choice situation. Stimulation induced a specific decrease in the intake of NaCl solution and had no effect on saccharin, acetic acid and quinine solutions and water. Total septal lesion or restricted lesions of medial or lateral septal areas induced hyperdipsia in rats. The lesioned rats, in a free-choice situation preferred NaCl, saccharin, as well as acetic acid solutions. This increase in acetic acid intake after lesion suggests that sour taste is also affected. Furthermore, there was no consumption of quinine solution before and after the lesion. This might be due to the presence of sweet tasting saccharin solution in this free-choice situation. These results indicate that the septal area causes aversion to NaCl intake, probably by inhibiting lateral hypothalamic neurons responsible for NaCl ingestion. The consumption of large quantities of saccharin, NaCl and acetic acid after the septal lesion suggests that the rats become overresponsive to taste factors in a free-choice situation.     

Early coping experience and later aversive conditioning in cats

Kittens were given differential early experience in order to compare an objective coping behavior with the result of an inescapable aversive experience. Separate groups of kittens were treated in a shock motivated runway task at either 4 or 12 weeks of age, by allowing one member of a weight matched sibling pair to acquire an escape behavior, while the other member was confined; a third subject served as a handled control. Escape behavior was significantly different for 4 and 12 week old subjects, since the older kittens reached a running asymptote within the first few shock trials. At 6 months of age, the subjects were tested for effects of differential early treatment; heart rate, respiration rate and amplitude, and somatic activity were measured during classical conditioning. While all groups gave evidence of acquisition in one or more response measures, only a potentiated heart rate response in 4 week kittens could be related to early experience. Heart rate did not differentiate escaping kittens from confined ones. Rather, heart rate was related to early treatment with shock, perhaps reflecting an increased tendency to react with a passive defensive response.     

Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas

Recent evidence suggests that kappa opiate receptors may play a key role in the regulation of appetite. Such evidence implies that kappa receptors might be localized within specific brain areas known to regulate ingestive behaviors. On the basis of this implication we employed an in vitro film autoradiographic technique using 3H-ethylketocyclazozine as ligand to identify putative kappa receptors within CNS "taste" nuclei and surrounding areas. Coronal cryostat sections of rat brain were incubated with ligand in the presence of D-Ala2, D-Leu5-enkephalin (DADLE) and morphine, apposed to LKB Ultrofilm for 60 days, processed and kappa receptor densities evaluated with the aid of a hand held photometer and video image analyzer. Highest kappa receptor densities were found within various gustatory and feeding sites including the rostral pole of the nucleus of the solitary tract, parabrachial nuclei, ventral posterior and medial portions of the thalamus, medial hypothalamus, medial nuclei of the amygdala and bed nucleus of the stria terminalis. Various other midline and medial limbic areas also showed significant kappa densities.     

The effect of drugs on the acquisition of stimulus control in a conditioned suppression procedure

Rats were trained to press a lever under a variable-interval (VI) schedule of water reinforcement. After stable responding had developed, a 4.5-KHz tone (CS) was conditioned classically to a 2.5-mA electric shock (US) in groups of animals which had been given various psychoactive drugs or saline. Twenty-four hours later, a stimulus generalization test was conducted in the absence of drug; during this session, tones that varied in frequency around 4.5 KHz were presented while the animals were responding under the VI schedule. In animals conditioned under saline, all tones (non-differentially) suppressed responding which, however, recovered gradually over time. This suppressive effect was eliminated by lysergic acid diethylamide (LSD; 0.2 and 0.32 mg/kg), cocaine (20 mg/kg), diazepam (2.5 mg/kg), lisuride (0.08 mg/kg), mescaline (20 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (4 mg/kg), and was attenuated by amphetamine (4 mg/kg), pentobarbital (15 mg/kg) and morphine (4 mg/kg). Atropine (10 mg/kg), scopolamine (1 mg/kg), clonazepam (0.5 mg/kg), and chlorpromazine (4 mg/kg) did not alter the suppressive effect of the tone. The serotonin antagonist BC-105 (6 mg/kg) reversed the effect of 0.2 mg/kg of LSD. These results suggest (1) that drug-induced stimuli may overshadow other (e.g., external) stimuli during classical conditioning and, (2) that drugs might affect behavior by altering processes (stimulus control or others) that do not simultaneously involve response or motor control.     

Anatomical disassociation of amphetamine's rewarding and aversive effects: An intracranial microinjection study

Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The persent study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 g/0.5 l per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed. Offprint requests to: N.M. White     

Effects of low-level microwave irradiation on amphetamine hyperthermia are blockable by naloxone and classically conditionable

In a series of experiments, we investigated the effects of pulsed low-level microwave irradiation on amphetamine-induced hyperthermia in the rat. Rats were irradiated in a 2,450-MHz cylindrical waveguide exposure system at 1 mW/cm², 2 s pulses, 500 pps, average SAR of 0.6 W/kg. Acute (45 min) exposure to microwaves attenuated amphetamine-induced hyperthermia. This effect was blocked by pretreatment of the animals with the narcotic antagonist naloxone. In another experiment, rats were subjected to ten daily sessions of microwave exposure (45 min/session). On day 11, amphetamine-induced hyperthermia was studied in the animals immediately after a session of either microwave or sham exposure. Similar to the acute effect, amphetamine-induced hyperthermia was attenuated in rats irradiated with microwaves (unconditioned effect). In the sham-irradiated animals we observed a potentiation of the amphetamine-induced hyperthermia, which was a conditioned effect of microwaves. Thus, the conditioned effect (potentiation) was opposite in direction to the unconditioned effect (attenuation). No tolerance developed to the unconditioned effect after subchronic exposure. Furthermore, both conditioned and unconditioned effects of microwaves on amphetamine-induced hyperthermia could be blocked by treatment with naloxone. These data suggest that (1) microwave irradiation may activate endogenous opioids, which in turn alter the actions of psychoactive drugs, and (2) the effect of microwaves on drug action can be classically conditioned. Offprint requests to: H. Lai