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M F Hawkins

Publications and source records attributed to M F Hawkins.

At least 19 recordsLinked to original sources
PubMed2000

Manipulation of central GABAergic and dopaminergic systems alters stress responding in the rat.

Activation of central GABA(A) systems with muscimol has been shown to facilitate stress responding and GABA is known to modulate central dopaminergic activity. To evaluate the possibility that this effect of muscimol may depend upon a dopamine mechanism we have tested the effect of intracerebroventricular coadministration of muscimol and the selective D(1) antagonist SCH 23390 on behaviors evoked by tail pinch stress. When injected by themselves muscimol (1.75 nmol) facilitated stress-evoked oral behavior while SCH 23390 (6-600 nmol) produced a dose-related suppression of oral behavior. Coadministration of muscimol and doses of SCH 23390 selected for producing no (6 and 30 nmol), or marginal (60 nmol), effects on stress responding resulted in a dose-related reversal of the increase in orality seen with muscimol alone. The results are consistent with the notion that stressful stimuli activate central GABA(A) systems which, in turn, enhance dopaminergic neurotransmission.

Animals↗
PubMed1999

Central GABA activation and behaviors evoked by tail-pinch stress in the rat.

Experiments were conducted to evaluate the possibility that central GABA(A) receptors are involved in the stress response of rats. Separate groups of animals were implanted bilaterally with cannulae in the lateral cerebral ventricle, substantia nigra, and anterior to the rostral margin of the substantia nigra. Microinjections of the GABA(A) agonist muscimol into each of these areas augmented the stress response evoked by moderate tail pinch. Although consistent changes in the amount of food eaten in response to stress were not observed, stress-evoked gnawing was significantly increased by muscimol at all three sites. Additionally, intraventricular muscimol resulted in an enhancement of stress-evoked oral stereotypy, revolution (escape behavior), and vocalization. The data suggest that a GABAergic component exists in the central mediation of stress. The results are discussed in regard to possible interactions between GABA and central dopamine systems.

Animals↗
PubMed1995

Some problems of high altitude in the 1930's: a world record attempt.

During the 1930's, nations competed for aircraft records in height, speed, and distance. During 1936 and 1937, attempts on the high altitude record were made by a Bristol Type 138 A, built under the sponsorship of the British Air Ministry. Designers had to face problems in three main areas: airframe design, engine power at extreme altitude, and life support for the pilot. The problems were met by developing a lightweight wooden airframe with a double supercharged Pegasus engine. A full pressure suit was evolved for the pilot, based on the experience of protection of divers in high pressure situations. This was accomplished by Professor J.B. Haldane working with Siebe Gorman Ltd. An altitude record of 49,967 ft was achieved by Sqd. Ldr. F.R.D. Swain on 28th September 1936. This was raised to 53,937 ft by Flt. Lt. M.J. Adam on 30th June 1937.

Altitude↗
PubMed1994

Effects in the rat of intranigral morphine and DAGO on eating and gnawing induced by stress.

Stress produced by pinching the tail is known to increase feeding behavior in rats, and endogenous opioids have been implicated in the mediation of this effect. We have reported previously that a nonspecific opioid antagonist and a mu-selective antagonist decrease this stress-induced eating (SIE) when they are microinjected into the substantia nigra (SN). The present study investigated the possibility that activation of opioid receptors in the SN might also alter SIE. Because oral stereotypy and nociception are affected by opioid mechanisms in the SN, measurements of gnawing and of tail flick and hot plate response latencies were also made. Bilateral injection of morphine (0.1-20 nmol) and the mu-selective agonist D-Ala2,N-Me-Phe4,Gly5-ol-enkephalin (DAGO; 0.03-1 nmol) increased response latency on the hot plate test and decreased gnawing produced by tail pinch. Tail flick latency and SIE were not affected. It is concluded that activation of opioid receptors in the SN does not produce an alteration in SIE as has been seen with opioid antagonists.

Amino Acid Sequence↗
PubMed1993

Bombesin-induced hypothermia in VMH-lesioned rats.

Microinfusion of bombesin into the lateral ventricles (LV) of rats pretreated with insulin or acutely deprived of food has been demonstrated to reduce core body temperature. Lesions of the ventromedial hypothalamus (VMH) have been shown to produce hyperphagia, hyperinsulinemia, and to alter serum metabolic fuels. The present study examines VMH lesions as a permissive event in bombesin-induced hypothermia in rats tested at normal ambient temperature. A between-group design was used to evaluate the effect of microinjections of bombesin (1, 10, 100 ng) into the LV of rats with bilateral VMH lesions or sham lesions. Core body temperature was recorded over a 240-min period. In animals with lesions of the VMH, hypothermia was demonstrated by 30 min after injection of the 10 ng and 100 ng doses; the hypothermia persisted for 120 min. The 1 ng dose had no effect on body temperature in VMH-lesioned animals. Animals that received sham lesions of the VMH did not demonstrate a reduction in core body temperature at the maximum effective dose (100 ng) of bombesin. These results suggest that some event(s) associated with bilateral VMH lesions acts as a permissive factor in the production of bombesin-induced hypothermia at normal ambient temperature.

Analysis of Variance↗
PubMed1992

Microinjection of opioid antagonists into the substantia nigra reduces stress-induced eating in rats.

Stress produced by pinching the tail has been shown to cause satiated animals to eat and to display oral stereotypies. Endogenous opioids and central dopamine systems have been implicated in the mediation of these effects. In order to test the possibility that the substantia nigra (SN) might be involved, the amount of food intake and gnawing produced by mild tail pinch were assessed following bilateral microinjections of opioid antagonists into the SN. Evaluations of nociceptive thresholds were also conducted using tail flick and hot plate tests. Eating induced by tail pinch was reduced by microinjections of the non-selective opioid antagonist naloxone (3, 10, 20 and 30 nmol) and by the mu-selective antagonist Cys2, Tyr3, Orn5, Pen7 Amide (CTOP) (1, 3 and 10 nmol). These effects on eating occurred in the absence of effects on gnawing. kappa- and delta-antagonists (10 nmol) had no effect on eating or gnawing. Naloxone did not alter either tail flick or hot-plate response latencies. The highest dose of CTOP increased response latency on the hot-plate test only. The results are interpreted as suggesting that the SN may be an important central site of action for opioid antagonists in reducing stress-induced eating. The possibility that the SN may be a central site mediating the effects of dopamine on this phenomenon is also discussed.

Animals↗
PubMed1990

Further studies of the effects of intranigral morphine on behavioral responses to noxious stimuli.

Bilateral intranigral microinjection of morphine produces dose-related and naloxone reversible analgesic-like effects on the hot-plate and tail-flick tests. The main objectives of the present studies were to further characterize the analgesic-like effects of intranigral morphine, to determine whether these effects were related to a general impairment of sensory or motor function, and to assess their anatomical specificity. The principal findings are: (1) intranigral morphine (10 micrograms) suppresses pain-related behavior without altering responses to a variety of non-noxious auditory, visual, and somatic stimuli, and without producing motor impairment; (2) movement of injector needles approximately 1 mm rostral, dorsal, or medial to the active nigral site significantly reduces the analgesic-like effect of morphine on the tail-flick test; and (3) electrolytic lesions confined to the nigra significantly reduced the analgesic-like effect of morphine on the hot-plate test. It is concluded that the analgesic-like effects of intranigral morphine are mediated by the substantia nigra and that these effects are specifically related to pain.

Animals↗
PubMed1990

Intranigral microinjection of neurotensin suppresses feeding in food deprived rats.

This study was conducted to determine whether the substantia nigra is involved in the anorectic effect of centrally administered neurotensin. Microinjection of neurotensin (2.5 - 10.0 micrograms) into the substantia nigra produced a significant suppression of feeding in 18 hour food deprived rats. To determine if the anorectic effect resulted from a general impairment of sensory-motor functioning, eight behaviors were measured in a separate study. Significant effects were found in only two of the eight behavioral categories (sniffing and eating), and only at the highest neurotensin dose (10.0 micrograms). These results suggest that the substantia nigra may be involved in the anorectic effect of neurotensin.

Animals↗
PubMed1989

Neurotensin-induced polydipsia: a structure-activity study.

Neurotensin (NT) and equimolar concentrations of NT fragments were microinjected into the lateral cerebral ventricle of water-deprived rats. NT (10 micrograms) increased water intake 146% in the first 15 min following injection. While NT1-11 and NT10-13 had no effect on water intake, NT8-13 increased water intake 101%. The polydipsia produced by NT8-13 was statistically equivalent to that produced by NT. The results are discussed in relation to a proposed model of the NT receptor.

Animals↗
PubMed1989

Evidence that physical dependence on morphine is mediated by the ventral midbrain.

Rats were given daily injections of increasing doses of morphine sulfate (40-100 mg/kg, s.c.), for 4 days. Twenty hours after the last injection of morphine, the animals received bilateral injections of naloxone (1-10 micrograms) into the substantia nigra, ventral tegmental area or sites 2 mm rostral, caudal or dorsal to the site in the nigra. Withdrawal signs were monitored for 20 min after the intracerebral injection. Naloxone administered into the nigra in morphine-dependent rats produced dose-dependent significant increases in wet dog shakes, irritability to touch, teeth chattering, diarrhea and locomotion, compared to morphine-dependent animals that received injections of saline into the nigra. The injection of naloxone (3 micrograms) into the ventral tegmental area of morphine-dependent animals, produced irritability to touch and diarrhea, compared to morphine-dependent controls that received saline in this region of the brain. Significant differences in withdrawal signs were observed between morphine-dependent animals, that received injections of naloxone (3 micrograms) into the nigra and those that received naloxone (3 micrograms) into the ventral tegmental area or rostral or caudal sites. No differences between the substantia nigra and the dorsal sites were observed. However, withdrawal symptoms were produced by injections of naloxone into the substantia nigra and ventral tegmental area, even when the guide cannulae were angled to avoid penetration of sites dorsal to these regions of the brain. Naloxone, injected into the ventral midbrain of non-dependent animals, produced no signs of withdrawal. These studies suggest that the ventral midbrain mediates physical dependence on morphine.

Animals↗
PubMed1989

Microinjection of neurotensin into the CNS induces hyperdipsia in the rat.

Neurotensin (NT) is a neuropeptide and putative neurotransmitter that has been shown to exert a variety of effects on digestive and ingestive processes. In order to address the possibility that NT might play a role in the regulation of water intake as well, the peptide was infused into the lateral cerebral ventricle, amygdala, ventral tegmental area, lateral hypothalamus, and preoptic area of the anterior hypothalamus of rats deprived of water for 16 hours. Neurotensin produced a significant and dose-dependent increase in water intake when injected into the ventricular system but had no effect when it was applied to the other brain sites. It was concluded that this peptide may play a physiological role in the control of water ingestion and that central sites of action remain to be determined.

Amygdala↗
PubMed1988

Evidence that the substantia nigra is a component of the endogenous pain suppression system in the rat.

The present study sought to determine whether opiate receptors in the substantia nigra may mediate antinociception produced by systemic morphine. Bilateral intranigral microinjection of naloxone-HCl (0.3-10 micrograms) suppressed the antinociceptive effects of systemically administered morphine sulfate (5 mg/kg, s.c.) on the tail-flick and hot-plate tests in a dose-related manner. Injection of naloxone (3 micrograms) into the ventral tegmental area did not alter antinociception produced by systemic morphine (5 mg/kg, s.c.). These findings support the argument that the substantia nigra is an essential, and previously unrecognized, component of the endogenous pain suppression system.

Analgesia↗
PubMed1988

Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia.

Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.

Analgesia↗
PubMed1987

Bilateral intranigral microinjection of morphine and opioid peptides produces antinociception in rats.

Bilateral intranigral microinjection of morphine produced dose-related and naloxone-reversible antinociceptive effects on the tail-flick and hot-plate tests. Intranigral injection of enkephalin had antinociceptive effects on both tests, and dynorphin had an antinociceptive effect on the hot-plate test. This is the first report of evidence that nigral opiate receptors may mediate antinociception.

Animals↗