Biomedical subjects

K B Franklin

Publications and source records attributed to K B Franklin.

At least 55 records · Page 3Linked to original sources

PubMed1987

Opposed locomotor asymmetries following lesions of the medial and lateral substantia nigra pars compacta or pars reticulata in the rat.

In animals with lesions in the medial or lateral portions of the substantia nigra pars compacta (SNC) amphetamine produces circling in opposite directions. The present study examined the relationships between lesion site and the direction of circling using glyoxylic acid histofluorescence to visualize DA cells. Lesions were produced by 6-hydroxydopamine (2-6 micrograms) or 0.05% ascorbate injected into the SN. After lesions in the medial SNC, amphetamine caused rats to circle ipsiversive to the lesion while after lateral SNC lesions rats circled contraversively. When the lesion extended to the middle of the SNC, or deeper into the SN pars reticulata (SNR), the direction of circling was unpredictable. When the damage produced by the cannula track and ascorbate injection was in the lateral SNR animals circled ipsiversively while medial SNR damage led to contraversive circling. Thus the medial and lateral SN, and the pars compacta and pars reticulata, are functionally antagonistic. This four way division of the SN is consistent with the topographic mapping of SNC to striatum and striatum to SNR.

Animals↗

PubMed1986

A dose-ratio comparison of mu and kappa agonists in formalin and thermal pain.

The effects of putative mu and kappa agonists, with and without naloxone, were compared in the formalin and tail flick tests in rats. The mu agonist sufentanil was more potent in the tail flick test than the formalin test while the opposite was true for the kappa agonist ethylketocyclazocine (EKC). MR2034 was equipotent in the two tests and in the tail flick test, analgesia decreased at high doses. The naloxone (0.1 mg/kg) dose-ratios (DR) for sufentanil and EKC were 3 to 7 times larger for the tail flick test than the formalin test. From this and other DR studies it is argued that in thermal pain tests, opioid analgesia is mediated primarily by mu receptors while in non thermal tests kappa effects predominate.

Analgesia↗

PubMed1986

The stress of a novel environment reduces formalin pain: possible role of serotonin.

Compared to rats that were given three daily sessions of habituation to a laboratory environment, non-habituated rats were behaviourally less reactive when pain was produced by 0.05 ml of 2.5% formalin injected s.c. in one hindpaw. This behavioural analgesia was equivalent to that produced by approximately 2.0 mg/kg morphine and was interpreted as analgesia induced by the stress of exposure to a novel environment. Methysergide (10 mg/kg) or 1-valine (200 mg/kg) alone, or combined with naloxone (0.1 or 2.0 mg/kg), reversed the effect of exposure to a novel environment. Naloxone itself had no significant effect. In habituated rats 1-valine reduced the response to formalin-induced pain whereas methysergide combined with naloxone increased it. It is concluded that analgesia induced by the stress of exposure to a novel environment depends on serotonin.

Animals↗

PubMed1986

Sympathetic control of tryptophan uptake and morphine analgesia in stressed rats.

Guanethidine treatment decreased morphine analgesia exhibited by restrained rats but had no effect on morphine analgesia exhibited by unrestrained rats or on baseline pain sensitivity. Guanethidine also prevented the rise in tryptophan uptake into the brain induced by the restraint stress. It is argued that the prevention of the stress-induced increase in brain tryptophan uptake is causal to guanethidine's attenuation of morphine analgesia exhibited by restrained rats, since the increase in brain tryptophan uptake has already been shown to be critical to this phenomenon. The blockade of the stress-induced increase in brain tryptophan uptake and morphine analgesia by guanethidine support the hypothesis that these effects depend upon sympathetic activity.

Analgesia↗

PubMed1986

Associative factors in the effects of morphine on self-stimulation.

These experiments tested the hypothesis that the suppressing and facilitating effects of morphine on intracranial self-stimulation (ICS) (measured 1 h and 3 h post-injection, respectively) are influenced by associative, non-pharmacological factors. Experiment 1 confirmed previous demonstrations that the facilitation of ICS by morphine (10 mg/kg) develops with repeated drug exposures. Once ICS facilitation had developed, the effect was mimicked by saline injection in most subjects. In a separate group of animals, previous exposure to morphine in the home cage prevented drug-induced facilitation of ICS. Tolerance to ICS suppression developed after repeated pairings of the drug and the ICS chambers, but not when the drug had previously been received in the home cage. Experiment 2 examined the effect of low (0.3, 1, 3 mg/kg) doses of chronic morphine on ICS. Facilitation was observed with 1 and 3 mg/kg, but only after repeated testing. Naloxone (0.1 and 1 mg/kg) failed to reverse facilitation in a number of these subjects. In Experiment 3, animals receiving their daily injections of morphine were allowed to self-stimulate only at 3 h post-injection (when ICS facilitation is usually maximal), rather than at 1 h and 3 h post-injection. ICS facilitation was not observed, even with repeated testing. These data indicate that the facilitation of ICS by morphine is the outcome of a learned association between drug administration and the ICS procedure, rather than the invariable result of opiate receptor activation. Repeated exposure to morphine is required for the initial establishment of ICS enhancement, but the subsequent expression of this behavior is not directly related to opiate receptor activity.

Animals↗

PubMed1986

Noncompetitive antagonism of morphine analgesia by diazepam in the formalin test.

The effects of diazepam on morphine analgesia dose effect curves in the formalin test and in two forms of the tail flick test were examined. In one form of the tail flick test the animals were restrained in wire restrainers (a stressful procedure) while in the other they were left free and briefly handheld for testing. Morphine analgesia in the restrained form of the test is known to depend on raphe magnus 5HT projections to the spinal cord while the other tests do not involve this system. Diazepam (0.2 and 1.0 mg/kg) noncompetitively antagonized morphine analgesia in the formalin test but had no effect on morphine analgesia in the tail flick test. It is concluded that diazepam does not antagonize morphine analgesia through its antianxiety action reducing the serotonergic response to stress. It is suggested that the sensitivity of the formalin test to diazepam antagonism of morphine analgesia may be of clinical significance since formalin test pain resembles postoperative pain in humans.

Animals↗

PubMed1985

Lesions of ventral tegmental dopamine neurons delay the development of tolerance to morphine catalepsy.

Selective lesions of the dopamine (DA) neurons of the ventral tegmental area (VTA) were found to substantially delay the development of tolerance to morphine-induced catalepsy, in comparison with sham-operated controls receiving morphine. Lesioned subjects receiving vehicle injections showed no catalepsy. The data suggest that tolerance to morphine catalepsy requires intact VTA DA neurons. Furthermore, since the acute cataleptic response was intact in lesioned animals, the data suggest that the mechanisms involved in the cataleptic response to morphine are dissociable from those which bring about tolerance to that response.

Animals↗

PubMed1985

6-OHDA lesions of the ventral tegmental area block morphine-induced but not amphetamine-induced facilitation of self-stimulation.

The biphasic effect of morphine on intracranial self-stimulation (ICSS) (suppression followed by facilitation) was examined in rats following injections of 6-OHDA or vehicle into the ventral tegmental area (VTA). During 7 days of chronic administration of morphine, sham-lesioned animals gradually developed tolerance to the rate-reducing effects of the drug and a concurrent sensitization to its rate-enhancing effects (measured 1 and 3 h post-injection, respectively). VTA lesioned rats showed neither tolerance to the rate suppression nor any facilitation of ICSS throughout testing. Amphetamine's facilitation of ICSS remained intact in all subjects. The lesion was restricted to the VTA cell bodies but produced a significant depletion of dopamine (DA) in both the nucleus accumbens and in the striatum. Morphine facilitation of ICSS is suggested to be dependent on an indirect opiate receptor-VTA DA cell interaction. It is also proposed that amphetamine facilitation of ICSS is a 'mass action' effect involving the full DA terminal area of the forebrain rather than a subregion of that area.

Animals↗

PubMed1985

An increase in tryptophan in brain may be a general mechanism for the effect of stress on sensitivity to pain.

The role of the stress-induced increase in the uptake of tryptophan in brain in opioid-induced analgesia was investigated by modifying the uptake of amino acid in brain with injections of competing amino acids. Blockade of analgesia by valine (200 mg/kg, i.p.) alone, and by valine and tyrosine (100 mg/kg, i.p.), but not by valine and tryptophan (100 mg/kg, i.p.), was taken to indicate that an increase in the uptake of tryptophan in brain was involved in opioid-induced analgesia. Morphine-induced analgesia exhibited by rats that were habituated to the laboratory and not restrained did not involve an increase in the uptake of tryptophan in brain. However, a mild form of restraint, or exposure to a novel environment interacted with morphine to induce analgesia which involved an increase in the uptake of tryptophan in brain. These stressors did not affect sensitivity to pain in the absence of morphine. Analgesia induced by 3 hr of restraint, which was preventable by naltrexone (1 mg/kg, s.c.) but not reversible by naloxone (1 mg/kg, s.c.), also involved an increase in the uptake of tryptophan in brain. It is concluded that the endogenous opioid-induced analgesia that is induced by stress alone and analgesia induced by stress interacting with morphine, both depend on an increase in the uptake of tryptophan into the brain.

Animals↗

PubMed1985

Opposite locomotor asymmetries elicited from the medial and lateral substantia nigra: role of the superior colliculus.

The present study investigated the role of the superior colliculus (SC) in the expression of opposing locomotor asymmetries elicited from the medial and lateral substantia nigra pars compacta (SNC). In experiment one it was found that amphetamine stimulated ipsiversive circling produced by unilateral SC lesions was additive with the ipsiversive circling produced by alpha-flupenthixol microinjections into the lateral SNC but was not additive with the contraversive circling produced by such injections into the medial SNC. Experiment two showed that the amphetamine stimulated ipsiversive circling produced by unilateral SC lesions was additive with the contraversive circling produced by lateral SNC lesions but was not additive with the ipsiversive circling produced by medial SNC lesions. Both experiments were taken to suggest that the striato-nigral-colliculus system is an output path for medial SNC derived circling but is not an output path for the opposing circling behavior derived from the lateral SNC.

Animals↗

PubMed1985

The role of the midbrain reticular formation in the expression of two opposing nigral denervation syndromes.

The present study investigated the role of the midbrain reticular formation (MRF) in the expression of opposing locomotor asymmetries elicited from the medial and lateral substantia nigra pars compacta (SNC). It was found that unilateral MRF lesions produced ipsiversive circling that was potentiated by amphetamine. Lateral SNC lesions produced contraversive circling while medial SNC lesions caused ipsiversive circling. When SNC lesions were combined with MRF lesions animals circled ipsiversively as they did with MRF lesions alone regardless of whether the SNC lesion was in the medial or lateral part of the SNC. Taken together, the results are consistent with the notion that a striato-nigral-MRF system is an output path for circling derived from both the medial and lateral SNC.

Animals↗

PubMed1984

Electrolytic raphe magnus lesions block analgesia induced by a stress-morphine interaction but not analgesia induced by morphine alone.

Morphine analgesia in the tail withdrawal test was examined in rats which had had lesions of the nucleus raphe magnus (NRM) or sham operations. Half of the rats were tested while restrained, whereas the other half were not restrained. In the sham-operated rats, restraint potentiated the analgesic response to morphine. Lesions of the NRM had no effect on unrestrained rats but reduced the morphine analgesia exhibited by restrained rats so that it was indistinguishable from that of unrestrained rats. The NRM seems to be involved in analgesia induced by an interaction of morphine and restraint but not in analgesia induced by morphine alone.

Animals↗

PubMed1984

Evidence that stress augments morphine analgesia by increasing brain tryptophan.

Morphine analgesia measured by the tail withdrawal test was examined in rats that were either restrained or left free during testing. It was found that restraint potentiated morphine analgesia and decreased the latency of the peak analgesic effect. Methysergide, a serotonin antagonist, and valine, which prevents the increase in brain tryptophan induced by restraint, blocked the effect of restraint on morphine analgesia. Valine did not alter analgesia in unrestrained rats. An increase in brain tryptophan uptake induced by stress is suggested as a possible mechanism by which stress can interact with pain modulation systems.

Analgesia↗

PubMed1984

Opposite locomotor asymmetries elicited from the medial and lateral SN by modulation of SN DA receptors.

In combination with systemic d-amphetamine (1 mg/kg), apomorphine or alpha-flupenthixol were unilaterally injected into either the medial or lateral substantia nigra pars compacta (SNC) of adult male hooded rats. Direction and magnitude of circling were measured. Alpha-flupenthixol (5 and 15 micrograms) injected into the medial SNC caused rats to circle contraversive to the injected side while laterally placed injections produced ipsiversive circling. Apomorphine (5 and 15 micrograms) induced ipsiversive circling when injected into the medial SNC but had no effect in the lateral SNC. The results show that nigrostriatal mediated circling can be induced by modulation of dopamine (DA) receptors in the SNC. Furthermore, the findings support the notion that lateral SNC DA neurons are functionally antagonistic to medial SNC DA neurons with respect to circling. The results also suggest that there may be medial-lateral SNC differences in the type of DA receptors.

Animals↗

PubMed1983

The influence of amphetamine on preference for lateral hypothalamic versus prefrontal cortex or ventral tegmental area self-stimulation.

Rats were trained to bar-press for intermittent reinforcement on a concurrent schedule offering self-stimulation (SS) at the animal's choice of one of two different brain loci. On the concurrent schedule, the relative reward value of the two reinforcers is evaluated by the way the subject divides its session time responding for these reinforcers, thus yielding a rate-free measure of reward in addition to response rate data. In animals with electrodes in the lateral hypothalamus (LH) and prefrontal cortex (PFC), amphetamine dose-dependently increased response rates as well as the proportion of time allotted to LH stimulation, demonstrating that the reward value of LH stimulation was increased relative to PFC stimulation. This finding supports the hypothesis that DA systems modulate the rewarding value of LH but not PFC SS, and it suggests that differing neural mechanisms underlie these two behaviors. In animals with LH/ventral tegmental area (VTA) implants, amphetamine had no effect on preference, although it produced an overall increase in rate. This suggests that the drug elevates the rewarding value of LH and VTA stimulation to a similar degree, and that the two regions may have a common DA-related reward substrate. Finally, it was found that when the two reinforcers were equally preferred (50% session time allotted towards each reinforcer), response rates for the two rewards were not necessarily equal. This confirms that SS response rate is not a simple function of reward magnitude.

Animals↗

PubMed1983

Differential effects of amphetamine isomers on SN self-stimulation: evidence for DA neuron subtypes.

The present experiment investigated the effects of varying doses of D- and L-amphetamine on intracranial self-stimulation (ICSS) in the medial or lateral substantia nigra (SN). It was found that the effects of D- and L-amphetamine on ICSS in the SN differ in these two sites. In the medial SN, there were no significant differences between the effects of D- and L-amphetamine on ICSS at any of the doses tested. Both isomers moderately facilitated ICSS with the peak effect at 0.8 to 2.0 mg/kg. By contrast, in the lateral SN, D-amphetamine produced a strong dose-dependent facilitation of ICSS which peaked at 2 mg/kg while L-amphetamine was ineffective below 7 mg/kg. Above 7 mg/kg L-amphetamine increased ICSS rates. The present experiments suggest that the medial and lateral SN are functionally different with respect to ICSS. The possibility that the present medial-lateral SN differences are mediated by two different types of dopamine cells is discussed. In addition, the effects of D- and L-amphetamine on ICSS in the lateral hypothalamus are discussed in light of the present findings.

Amphetamine↗

PubMed1982

Dopamine mediates ipsi- and contraversive circling elicited from the substantia nigra.

It was found that ipsiversive and contraversive circling could be induced by imposed stimulation of the lateral and median portions of the substantia nigra pars compacta (SNC), respectively. Stimulation of more ventral sites in the substantia nigra (SN) did not elicit circling. Pimozide, a dopamine (DA) antagonist, dose dependently blocked both ipsiversive and contraversive circling induced by imposed stimulation of the SN, but did not alter circling elicited from the non-dopaminergic cerebral peduncle. However, amphetamine, a catecholamine agonist, did not facilitate stimulation-induced circling elicited from the SN possibly because it releases DA on both sides of the brain and thus fails to exaggerate the imbalance of activity produced by stimulation. Taken together these results suggest that DA is involved in SN mechanisms mediating both ipsiversive and contraversive stimulation induced circling and provide further evidence that the lateral SN may be functionally antagonistic to the medial SN.

Amphetamine↗

PubMed1982

Effects and interactions of naloxone and amphetamine on self-stimulation of the prefrontal cortex and dorsal tegmentum.

Naloxone (0.1 to 10 mg/kg) caused a dose-dependent depression of self-stimulation of the medial prefrontal cortex (PFC) lateral hypothalamus (LH) and a region in the dorsal tegmentum lateral to the central gray (DT). The DT contains many enkephalin fibers and is a site for stimulation-produced analgesia, while the PFC contains little enkephalin and does not support stimulation-produced analgesia. However, self-stimulation rates of the PFC, DT and LH were all equally depressed by naloxone. In order to study possible opiate-dopamine interactions, we examined the effects of naloxone on the facilitatory effects of D- and L-amphetamine (1.0 mg/kg) on self-stimulation of the DT and PFC. If amphetamine mildly facilitated self-stimulation (L-amphetamine on DT self-stimulation and D-amphetamine on PFC self-stimulation) then the addition of naloxone was without effect. If amphetamine greatly increased self-stimulation (D-amphetamine on DT self-stimulation), naloxone caused a depression of the amphetamine effect. It is argued that naloxone's effects in this and other reports reviewed is related to the level of self-stimulation performance, and not to the level of enkephalin at the self-stimulation site, nor to amphetamine's effects on dopamine activity.

Amphetamine↗