Biomedical subjects

D M Atrens

Publications and source records attributed to D M Atrens.

At least 37 records · Page 2Linked to original sources

PubMed1990

Stressor-like effects of FG-7142 on medial prefrontal cortex self-stimulation.

The effects of uncontrollable stress and the anxiogenic beta-carboline FG-7142 were compared on rats bar-pressing for electrical stimulation of the medial prefrontal cortex (MPC). One minute of restraint stress produced an immediate 20% increase in response rates. A significant facilitation was also evident 24 and 48 h later. Similarly, FG-7142 (10 mg/kg) produced an immediate 20% elevation of self-stimulation rates and a significant facilitation 24 and 48 h following administration. Lower (3 mg/kg) and higher (20 mg/kg) doses of FG-7142 caused immediate decreases in MPC self-stimulation and no significant long-term effects. These results agree with previous findings that FG-7142, administered at certain doses, may mimic the effects of exposure to uncontrollable stress.

Animals↗

PubMed1990

Idazoxan increases rough-and-tumble play, activity and exploration in juvenile rats.

The effects of idazoxan, an alpha-2 noradrenergic antagonist, on play and open field behavior were assessed in juvenile rats. Play was assessed in two separate paradigms. Initially, juvenile rats were housed individually and given a daily 5 min opportunity to play with a responsive partner. Idazoxan (1-8 mg/kg) increased pinning, an indicator variable of play, but did not affect the frequency of dorsal contacts, an index of play solicitation. When rats were tested in a separate test for play solicitation using an unresponsive play partner, idazoxan increased all three measures of play solicitation. Idazoxan increased activity and exploration when rats were tested in an open field, suggesting that the effects of idazoxan on play may be due to an increase in behavioral arousal and/or attention. These data are consistent with a modulatory role for norepinephrine in the control of behavior.

Animals↗

PubMed1990

Metabolic effects of neuropeptide Y injected into the sulcal prefrontal cortex.

The metabolic effects of 10, 39 and 156 pmol doses of neuropeptide Y (NPY) injected into the sulcal prefrontal cortex (SPC) were investigated in an open-circuit calorimeter. The 39 pmol dose produced a large and long lasting increase in respiratory quotient indicating both increased utilization of carbohydrate as an energy substrate and the synthesis of fat from carbohydrate. The 10 and 39 pmol doses produced an inhibition of energy expenditure that was still evident 24 hours following the 10, but not the 39 pmol, dose. These energy expenditure effects appeared to reflect an inhibition of thermogenesis as they were not systematically related to changes in locomotor activity. In separate tests, 39 pmol NPY reliably enhanced food intake. This combination of effects, namely increased carbohydrate utilization, fat synthesis and food intake with reduced energy expenditure, shows NPY to be a potent anabolic force. In addition, these results indicate both the functional significance of NPY at a cortical level and the important role of the SPC in the control of energy balance.

Animals↗

PubMed1989

Footshock stress facilitates self-stimulation of the medial prefrontal cortex but not the lateral hypothalamus in the rat.

The effects of stress on self-stimulation were investigated by exposing rats to either controllable, uncontrollable or no footshock. Both controllable and uncontrollable footshock increased medial prefrontal cortex self-stimulation rates immediately as well as 24 h following treatment. Controllable footshock produced a greater enhancement than uncontrollable footshock. In contrast, self-stimulation of the lateral hypothalamus was unaffected by either footshock treatment. These results are interpreted with reference to the neurochemical response of the mesocortical dopaminergic system to acute stress.

Animals↗

PubMed1989

Effects of norepinephrine infused in the paraventricular hypothalamus on energy expenditure in the rat.

The metabolic effects of norepinephrine (NE), when infused into the paraventricular nucleus of the hypothalamus (PVN), were examined using indirect calorimetry. In two separate experiments, it was found that NE infused into the PVN reduced energy expenditure in freely moving rats. While NE also reduced motor activity, these reductions were not statistically significant. Reductions in voluntary motor activity were not necessary for a reduction in energy expenditure, as NE still reduced energy expenditure in rats that were lightly sedated. Clonidine, but not L-phenylephrine, mimicked the hypometabolic effect of NE, suggesting an action at alpha 2 receptors. Infusions of NE were also found to increase blood glucose shortly after infusion, although the specificity of this effect is questionable. Taken together, these data suggest that activation of noradrenergic neurons within the PVN results in a metabolic shift towards energy conservation.

Animals↗

PubMed1989

The intrinsic and interactive effects of RO 15-4513 and ethanol on locomotor activity, body temperature, and blood glucose concentration.

The ability of the putative ethanol antagonist RO 15-4513 to antagonize ethanol - induced hypoactivity, hypothermia and hyperglycemia was investigated in rats. Although RO 15-4513 produced hypoactivity by itself, it attenuated ethanol - induced hypoactivity. This antagonism suggests that ethanol - induced hypoactivity is mediated by the GABA-benzodiazepine receptor complex which is thought to be the site of action of RO 15-4513. In contrast, although RO 15-4513 produced hypothermia by itself, it had no significant effect on ethanol - induced hypothermia. This suggests that the hypothermic effect of ethanol is not mediated by the GABA-benzodiazepine receptor complex. The fact that RO 15-4513, ethanol and the vehicle all produced hyperglycemia suggests a common stress effect and does not permit any firm conclusions to be drawn as to the interaction between ethanol and RO 15-4513 in modulating glycemic responses. These data indicate that the ethanol antagonism of RO 15-4513 is primarily confined to ethanol's behavioural effects and that ethanol's behavioural and physiological effects are mediated by neurochemically distinct mechanisms.

Analysis of Variance↗

PubMed1989

Environment-specific conditioning produced by electrical stimulation of the lateral hypothalamus.

Rats received noncontingent electrical stimulation of the lateral hypothalamus on one side of a place preference apparatus and no stimulation on the other side. Subsequently, when allowed access to both sides, the rats spent more time on the side associated with stimulation. This change in preference was only found in rats receiving stimulation in the side least preferred prior to conditioning trials. It was further shown that the place preference conditioning procedure produces increased locomotor activity. Thus, the place preference obtained was not an artifact produced by a conditioned freezing response. These data suggest that both the reinforcing and activating effects of lateral hypothalamic stimulation may be conditioned to a specific environment. Some methodological problems of the place preference paradigm are discussed.

Animals↗

PubMed1989

Controllability of prestimulation of the medial prefrontal cortex determines the facilitation of self-stimulation and kindled seizures.

Electrical stimulation of the medial prefrontal cortex (MPC) was administered according to the triadic design typically used to demonstrate learned helplessness. Three groups received either controllable, uncontrollable or no stimulation during the pretreatment phase. The effects of this pretreatment on the acquisition of self-stimulation at the same electrode site were investigated in the second phase of the experiment. Relative to unstimulated controls, both controllable and uncontrollable prestimulation facilitated the acquisition of self-stimulation and produced higher self-stimulation rates. In addition, compared with controllable stimulation, pretreatment with uncontrollable stimulation produced a greater facilitation in self-stimulation rate. The unambiguous demonstration of a behavioural facilitation produced by pretreatment with uncontrollable stimulation is, effectively, the inverse of the typical learned helplessness finding. It was also found, in the second phase of the experiment, that 6 of the 7 rats previously exposed to uncontrollable stimulation developed full class 5 seizures. No behavioural evidence of kindling was seen in any of the other rats or during the prestimulation procedure. These data are interpreted in terms of kindling and stress effects both proximal and distal to the site of stimulation.

Animals↗

PubMed1989

Insulin increases energy expenditure and respiratory quotient in the rat.

The effects of insulin on energy expenditure are a matter of dispute. Various authors have reported increases or decreases. Irrespective of their nature, it is not clear whether the effects of insulin on energy expenditure are secondary to insulin-induced hypoglycemia or changes in motor activity. The present study investigated the acute effects of insulin on energy expenditure, energy substrate utilisation, motor activity and blood glucose levels. Four U/kg of fast acting insulin had no effect on any of the metabolic or motor activity measures in spite of producing a 30% reduction in blood glucose levels. In contrast, 8 U/kg of insulin increased energy expenditure and respiratory quotient, with the latter effect indicating increased reliance on carbohydrates as a source of energy. This dose reduced blood glucose levels by 68%, yet had no significant effect on motor activity. Insulin, therefore, enhances thermogenesis and carbohydrate utilisation in a manner that can be dissociated from any effect on motor activity. These effects occur at a high dose and they are not counteracted by even massive hypoglycemia. It, therefore, appears that in terms of energy expenditure insulin may be characterised as catabolic, whereas in terms of substrate utilisation it may be characterised as anabolic.

Animals↗

PubMed1987

Hypothalamic modulation of thermogenesis and energy substrate utilization.

The metabolic effects of electrical stimulation of the hypothalamus were investigated using indirect calorimetry. Stimulation of either the ventromedial hypothalamic nucleus (VMH) or the lateral hypothalamic area (LH) increased both respiratory quotient (RQ) and energy expenditure (EE) in 23 lightly anesthetized rats. The use of a muscle relaxant to reduce motor activity and a regression analysis on the residual activity showed that the metabolic changes were independent of motor activity following LH stimulation. The increased RQ indicates that stimulation increased the dependence on carbohydrates as an energy substrate. The increased EE indicates that the LH modulates EE by mediating thermogenesis. The interpretation of the metabolic changes in RQ and EE following VMH stimulation is complicated by the fact that there were significant relationships between residual activity and metabolic changes in the sedated rats with VMH electrodes. Together, these data suggest that the hypothalamus regulates body weight by controlling energy expenditure, as well as energy intake. At the same time, hypothalamic activity influences which substrate the rat uses for energy.

Animals↗

PubMed1985

Development of hypoglycemia and hyperglycemia as a function of number of trials in insulin conditioning.

A neutral environment paired with insulin injections can develop the capacity to elicit glycemic changes. However, both conditioned hypoglycemia and conditioned hyperglycemia have been reported under apparently similar circumstances. The present study examined conditioned glycemic changes as a function of the number of conditioning trials and the novelty of the conditioning environment. Adult, male Wistar rats were injected with either insulin or physiological saline every second day, in either a novel or a familiar environment. On the test day, all rats were injected with saline and blood was collected 20 minutes later for determination of glucose levels. In rats given insulin in the novel environment, conditioned hypoglycemia was observed after two trials but was replaced by conditioned hyperglycemia after five trials. No conditioning at all occurred in the familiar environment. The two conditioned responses observed were interpreted as reflecting two unconditioned responses brought about by insulin--a hypoglycemic response to the central detection of insulin, and a hyperglycemic response to the detection of (insulin-induced) hypoglycemia. Taken in conjunction with previous experiments in which both conditioned response patterns have occurred, the present results suggest that the homeostatic response of hyperglycemia can become strong enough to overcome the initial conditioned response of hypoglycemia, but that its establishment depends on the use of a novel conditioned stimulus and a larger number of conditioning trials.

Animals↗

PubMed1985

Hypothalamic modulation of energy expenditure.

The acute effects of electrical stimulation of the hypothalamus on energy expenditure as measured by indirect calorimetry were investigated in 20 unanaesthetized rats. Thirty sec of stimulation increased both O2 consumption and respiratory quotient (R.Q.). The largest magnitude hypermetabolic response (39% mean peak increase in O2 consumption) was produced by stimulation of the ventromedial hypothalamic nucleus. Stimulation of the lateral hypothalamus produced hypermetabolic effects similar to but smaller than those produced by medial stimulation. A number of considerations suggest that the hypermetabolism is not secondary to changes in motor activity, carbohydrate utilization or blood glucose levels. Consequently, these data suggest that the hypothalamus modulates energy expenditure through changes in non-shivering thermogenesis. These metabolic changes may modulate the effects of various hypothalamic manipulations on body weight.

Animals↗

PubMed1985

Effects of chronic lithium, amitriptyline and mianserin on glucoregulation, corticosterone and energy balance in the rat.

Major negative side-effects reported for mood-stabilizing and antidepressant drugs in humans are excess weight gain and carbohydrate craving. The aim of the present study was to establish whether the rat could usefully be employed in investigation of these phenomena. Three experiments investigated the effects of chronic lithium (40 mg/kg LiCl), amitriptyline (2.5 mg/kg), mianserin (2.5 mg/kg) and saline administration (15-20 days, one subcutaneous injection/day) on body weight, food intake and fluid intake. Water and food cubes were provided in all experiments. Additionally available, as separate fluid sources, in Experiment 2 were 24% sucrose and 0.6% saccharin and in Experiment 3, 0.6% saccharin. Blood was collected for plasma glucose and insulin determinations 20-24 hours after the final injections. Lithium administration resulted in a marked increase in weight gain but only if both sucrose and saccharin were available (Experiment 2). Saccharin intake was increased with lithium treatment as was total caloric intake with sucrose available. Amitriptyline induced a sweetness craving; however, weight gain was somewhat depressed with just cubes available (Experiment 1) and only normalised by the additional availability of sucrose and saccharin (Experiment 2). With amitriptyline, total caloric intake was never different from controls. Weight gain was slightly suppressed and caloric intake slightly elevated by mianserin but importantly the two effects combined for a decrease in metabolic efficiency which was particularly exaggerated under the condition of carbohydrate availability (Experiment 2). Lithium and amitriptyline both produced hyperinsulinemia with normoglycemia whether or not the rate of weight gain was changed and whether or not intake was increased. Corticosterone levels were elevated by all drug treatments in Experiment 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗

PubMed1984

The effect of electrical stimulation of the hypothalamus on continuously-monitored blood glucose levels.

The effects of hypothalamic stimulation on blood glucose levels were investigated in unanaesthetised rats with intracardiac catheters directly connected to a continuous glucose analyzer. Thirty sec of low level electrical stimulation produced hyperglycemia at 23 of the 34 sites stimulated. At the remaining 11 sites the electrical stimulation produced no changes in blood glucose levels. The hyperglycemia could be dissociated from the changes in motor activity produced by the stimulation. The highest probability of producing hyperglycemia was found at ventro-lateral sites although hyperglycemia was also observed after stimulation of dorsal and medial sites. Apart from this medio-lateral difference in the density of sites at which stimulation produced hyperglycemia, the effects were not well differentiated anatomically. In addition, in terms of latency, peak magnitude and duration of the hyperglycemia, stimulation of the various hypothalamic subdivisions appeared to be functionally equivalent. Thus with respect to hypothalamic involvement in the maintenance of blood glucose levels the present stimulation analysis suggests a medio-lateral functional similarity which is very different from the medio-lateral reciprocity of lesion effects on ingestive behaviour and body weight.

Animals↗

PubMed1983

Dissociating the determinants of self-stimulation.

Four experiments were conducted to elucidate the determinants of the initiation of and escape from electrical stimulation of the lateral hypothalamus under several different reinforcement schedules. The first experiment of this series used correlational and factor analytic techniques to show that, under continuous reinforcement, the vigour of initiation is determined more by forcement than by positive reinforcement. Forcement is defined as all of the performance changes directly elicited and potentiated by the stimulation. Escape is determined by adaptation of positive reinforcement, not by negative reinforcement or aversion. Continuous reinforcement schedules are, therefore, not appropriate for studying either the positive or negative reinforcement produced by brain stimulation. The second experiment used fixed-interval reinforcement schedules to eliminate the effects of forcement on initiation and adaptation of positive reinforcement on escape. Parametric manipulations indicate that activity in the positive reinforcement and escape systems is a simple function of stimulation charge. The combination of parameters which make up a given charge is of relatively little importance. However, the positive reinforcement system becomes maximally activated at far lower charges than does the escape system. The third experiment used a T-maze technique to show that, after 5 sec, anterior hypothalamic stimulation becomes negatively reinforcing, but posterior hypothalamic stimulation does not. Since the escape from posterior hypothalamic stimulation on a fixed-interval schedule can be dissociated from both negative reinforcement and adaptation of positive reinforcement, it is suggested that such escape is reinforced by a positive process triggered by the offset of stimulation (OFF positive reinforcement). The fourth experiment showed that stimulation trains longer than 10 sec are significantly less positively reinforcing than much shorter trains. This reduction in positive reinforcement confirms the development of negative reinforcement in long trains of hypothalamic stimulation, even at posterior electrodes. Negative reinforcement appears to be as general a property of hypothalamic stimulation as is positive reinforcement. Thus, depending on the reinforcement schedule and electrode site, the initiation of lateral hypothalamic stimulation may be determined by ON positive reinforcement, OFF positive reinforcement and forcement. Escape may be determined by OFF positive reinforcement, adaptation of positive reinforcement and negative reinforcement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1983

Self-stimulation of the nucleus accumbens and some comparisons with hypothalamic self-stimulation.

Rats were trained to respond for electrical stimulation of the nucleus accumbens (ACB) or lateral hypothalamus (HYP) in a shuttle-box apparatus. Whereas the HYP rats showed rapid acquisition and stabilization of performance, the ACB rats were slow to learn the task and commonly took longer than 20 daily sessions to stabilize. Once stabilized, both groups responded with similarly vigorous performance. All rats displayed a predominantly locomotor behaviour, which was almost totally devoid of exploratory behaviours typically associated with self-stimulation. The absence of stimulus-bound behaviours was particularly notable in the ACB group. These rats, but not the HYP rats, showed an increase in the latency to initiate stimulation during the daily 25-min test sessions. Depriving the animals of a single self-stimulation session caused a decrease in the latency of ACB rats to initiate on the following day while having no effect on the HYP rats. All ACB rats gradually developed convulsive seizures during the first 3 weeks of testing which subsequently became more frequent and severe. None of the HYP rats showed any involuntary motor effects. The results show that ACB self-stimulation is a very different phenomenon to HYP self-stimulation, and suggest that, in addition to reward and aversion, ACB self-stimulation may involve a stereotyped ritual controlled partly by adaptation and conditioning.

Animals↗

PubMed1983

Ethanol preference following hypothalamic stimulation: relation to stimulation parameters and energy balance.

Rats were given 5, 10, 20 and 30 min daily sessions of lateral hypothalamic stimulation. Approximately half of the rats showed a large and highly significant increase in their total intake of and preference for 10% v/v ethanol which was continuously available in their home cages. In terms of latency, total consumption and preference for ethanol, 10 min of daily stimulation produced a much greater enhancement than did 30 min. The ethanol drinking rats used more energy per unit of body weight which suggests that the stimulation and/or the ethanol itself may have increased energy expenditure. Simply changing the diet from powdered chow to identical composition pellets produced a large reduction in both total ethanol intake and preference. Reinstating the powdered diet produced a rapid reinstatement of ethanol drinking. These data are discussed in terms of ethanol's role in modulating stimulation induced changes in energy balance.

Alcohol Drinking↗

PubMed1982

Dopaminergic and noradrenergic inhibition of hypothalamic self-stimulation: differentiation of reward and performance effects.

Dopaminergic and noradrenergic inhibition of lateral hypothalamic self-stimulation was investigated in a new signalled, discrete-trials shuttle-box paradigm. The differential inhibitory effects of drugs and stimulation frequency reductions within small blocks of trials differentiate reward inhibition from a variety of performance deficits. They further differentiate among the deficits produced by fatigue, sedation, dyskinesias, akinesia and sensory disruption. Pimozide's selective inhibition of the first response within each block of trials shows that its inhibition of self-stimulation is not due to either an inhibition of reward or to a general performance deficit. Instead, it suggests that pimozide specifically inhibits the initiation of motor responding. Pimozide-induced akinesia appears to be partly reversible by hypothalamic stimulation. Thus the pimozide data do not support a role for dopamine in mediating brain-stimulation reward. Since the inhibitory effects of clonidine were very similar to those of pimozide, it is suggested that clonidine also produces a stimulation-reversible akinesia. Thus the clonidine data do not support a role for noradrenaline in mediating brain-stimulation reward. LU 5-003, which selectively inhibits the presynaptic reuptake of noradrenaline, inhibited self-stimulation in almost exactly the same way as did reducing reward by reducing stimulation frequency. These data do support a primary role for noradrenaline in mediating brain-stimulation reward. However, it is suggested that LU 5-003 inhibits self-stimulation, not by inhibiting reward, but by enhancing reward and making the electrical stimulation superfluous.

Animals↗