Unilateral substantia nigra lesions and schedule-induced polydipsia

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the substantia nigra (SN) on schedule-induced polydipsia (SIP). Lesions were made in either the "dominant" or "non-dominant" hemisphere as defined by an amphetamine rotation test. It was found that unilateral lesions of either the "dominant" or "non-dominant" SN significantly reduced SIP and also significantly impaired somatosensory responsiveness as indicated by the "tactile extinction test." Somatosensory neglect was significantly greater following a lesion in the "dominant" hemisphere than "non-dominant" hemisphere.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26418/1/0000505.pd

Individual differences in non-regulatory ingestive behavior and catecholamine systems

Animals that eat and/or drink in response to electrical stimulation of the lateral hypothalamus (ESLH-pos) are more responsive to both schedule-induced polydipsia (SIP) tests and a series of amphetamine (AMPH) injections than animals that do not exhibit these behaviors (ESLH-neg). Moreover, prior exposure to the behaviorally activating SIP experience, or to AMPH, permanently transformed the ESLH-neg animals into animals that reliably ate or drank during ESLH. Prior treatment with AMPH also increases the water consumed during subsequent SIP tests. Thus, initial of induced differences in sensitivity to activating experiences can determine behavioral propensities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25493/1/0000034.pd

On drinkometers: Problems and an inexpensive photocell solution

Electronic contact switches may interfere with measurements of taste discrimination and also the ability to utilize physiological recording or stimulation techniques simultaneously. An inexpensive and simply constructed photocell-drinkometer solution to both these problems is presented.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33523/1/0000021.pd

Strain differences in eating and drinking evoked by electrical stimulation of the hypothalamus

Electrical stimulation of the lateral hypothalamus (ESLH) has been shown to produce individual response differences that cannot be attributed to the neuroanatomical locus of the electrode. The purpose of the present experiment was to investigate strain differences in the incidence of eating and drinking evoked by ESLH. The responses of 49 Long-Evans and 51 Sprague-Dawley male rats implanted with bilateral hypothalamic electrodes were studied. Animals from these two strains do not differ in their normal food or water consumption. Analysis of the responses to ESLH demonstrated that a significantly greater number of Long-Evans rats ate food and/or drank water during ESLH than did the Sprague-Dawley rats. These results could not be attributed to differences in electrode placements, or rearing conditions. In addition to strain differences, the importance of individual differences within each strain was demonstrated by the fact that both electrodes in a given animal commonly evoked the same behavior. Hypotheses to explain these results are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24451/1/0000725.pd

Changes in responsiveness to mu and kappa opiates following a series of convulsions

After a series of seven electroconvulsive shocks, mice (C57BL/6J) showed a marked change in their response to opiates. Although very large doses of mu agonists induce convulsions in normal control mice, our evidence indicated that this was accomplished through nonopiate mechanisms: they could not be blocked by naltrexone and the pattern of drug potencies (codeine > morphine > levorphanol) was not consistent with an opiate response. In contrast, after electroconvulsive shock small doses of mu agonists induced convulsions that could be blocked by naltrexone and the pattern of drug potency (levorphanol > morphine > codeine) was consistent with an opiate mechanism. Kappa drugs, on the other hand, produced convulsions in both control and ECS animals, although there was an enhanced responsiveness in the latter. Furthermore, the convulsions produced by kappa drugs were blocked by naltrexone and showed stereoselectivity in both control and ECS animals. The changes in responsiveness to mu and kappa opiates cannot be explained on the basis of a general increase in seizure susceptibility, as sensitivity to the nonopiate convulsant, strychnine, was not enhanced after electroconvulsive shock. The results point to a qualitative change in response to mu agonists after electroconvulsive shock, but only a change in sensitivity to kappa agonists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25549/1/0000091.pd

Convulsions may alter the specificity of kappa-opiate receptors

Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that eletroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26156/1/0000233.pd

Long-term inhibition of kindled seizures by brain stimulation

It was concluded from previous studies that prior stimulation produced a long-lasting inhibition of kindled seizures only when a series of convulsions were evoked. The present study describes a brain stimulation procedure capable of producing a long-lasting inhibition of kindled convulsions without evoking prior convulsions of EEG afterdischarge. Electrodes were implanted in the amygdala of rats, which were then kindled to a criterion of five successive tonic-clonic convulsions. After kindling, the animals were exposed to a regimen of intermittent amygdala stimulation, which was gradually increased in intensity in small incremental steps from a point just below the convulsion threshold to an intensity above the original kindling current. Using this procedure, it proved possible to administer high stimulation intensities without evoking any behavioral convulsions or EEG afterdischarges. Subsequent to this inhibitory procedure, amygdala stimulation did not evoke convulsions or EEG seizures for as long as 7 days. Additional studies tested the relative effectiveness of different stimulation rggimens and parameters for producing long-lasting inhibition of kindled seizures. The magnitude of the incremental intensity steps, the interstimulus interval, and the intensity of stimulation all proved to be relevent. We concluded that long-lasting inhibition of kindled seizures could be produced by prior stimulation that did not evoke seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24000/1/0000249.pd

Morphine responsiveness and seizure proneness

Previous research demonstrated that following amygdala kindling, animals showed a heightened sensitivity to morphine's convulsive effects and an exaggerated Straub tail response. These effects were evident to 3 months after their last convulsion and could be blocked by naloxone pretreatment. The present paper extends these findings by demonstrating that animals given metrazol or electroshock (ECS) convulsions also showed an enhanced morphine response that was blocked by naltrexone. Both metrazol- and ECS-treated animals convulsed in response to doses of morphine that produced little or no effect in control animals. In addition, it was shown that brain damage induced by electrode implantation or neocortex penetration by skull screws also increased an animal's sensitivity to morphine even in the absence of prior convulsions. This effect, however, could not be blocked by naltrexone. Finally, as opiate receptors vary with the diurnal rhythm, we determined that following amygdala kindling, animals are more sensitive to morphine's convulsive action during their dark phase when receptor number and sensitivity are highest. The results indicated that seizure proneness, whether induced by a history of prior convulsions or brain damage, increased sensitivity to morphine. This effect may be due to a change in opiate receptors only when prior convulsions have occurred.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24747/1/0000169.pd

What psychological processes mediate feeding evoked by lateral hypothalamic electrical stimulation?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29232/1/0000287.pd

Individual differences in sexual responsiveness to estrogen and progesterone in ovariectomized rats

Individual differences among 83 ovariectomized rats in behavioral responsiveness to estrogen were measured by scoring the quality of sexual receptivity induced by injections of estradiol benzoate (EB) and progesterone (P). The P dose remained constant but the quantity of EB administered was systematically reduced over successive weeks until lordosis behavior could no longer be elicited. This EB dose was considered threshold. This sequence of weekly hormone injections and receptivity tests was repeated to assess the reliability of our procedures. Animals had thresholds of either 2.0, 1.0 or 0.5 [mu]g/kg EB on both tests; the correlation between threshold values on the two tests was high (r=0.66; p<0.001). Sixty-two females were used to determine the facilitating effects of various quantities of P following EB treatment. Subgroups were tested after the E alone and again after one of 6 P doses. Zero, 20, 50 and 100 [mu]g P failed to elevate receptivity scores significantly; both 250 and 500 [mu]g P had significant facilitating effects. The results demonstrated that individual differences in EB sensitivity can be measured reliably, and a further analysis also suggests similar individual differences in P responsiveness. Our threshold determination procedures provide a useful technique for measuring the effects of various experimental manipulations on the hormone sensitivity of brain mechanisms which regulate estrous behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34132/1/0000416.pd