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D K Pitts

Publications and source records attributed to D K Pitts.

31 records · Page 2Linked to original sources
PubMed1987

Reciprocal pre- and postsynaptic actions of cocaine at a central noradrenergic synapse.

Single-unit microelectrode studies were conducted to test the effects of systemic cocaine HCl on spontaneously firing single noradrenergic locus ceruleus (presynaptic) and cerebellar Purkinje (postsynaptic) neurons in rats in vivo. The spontaneous neuronal activity of all locus ceruleus neurons was inhibited by cocaine in a dose-dependent manner (0.5 to 2 mg/kg). These doses of cocaine elicited a predominant activation of postsynaptic Purkinje neurons. No effect of cocaine on neuronal action potential amplitude or slope was observed. Similar doses of the local anesthetic agent, procaine, did not affect action potential amplitudes or slopes of either locus ceruleus or Purkinje neurons. In addition, although cocaine elicited a significantly greater absolute change in the discharge rate of locus ceruleus neurons than of Purkinje neurons, the effects of procaine on those neurons were not significantly different from each other. The inhibition of locus ceruleus neurons by cocaine was significantly attenuated by pretreatment either with the alpha 2-adrenoceptor antagonist, yohimbine, or with reserpine. The activation of Purkinje neurons by cocaine was also significantly attenuated by reserpine pretreatment. Systemic cocaine administration (1 mg/kg, i.v.) did not potentiate the inhibitory effects of either locus ceruleus stimulation or local iontophoretic application of norepinephrine on Purkinje neuron discharge rate. We conclude that cocaine potently inhibits locus ceruleus neurons and this effect probably elicits Purkinje cell activation through disinhibition.

Action Potentials↗
PubMed1987

Cocaine modulation of central monoaminergic neurotransmission.

Extracellular microelectrode studies were conducted to test the effects of cocaine HCl on the activity of spontaneously firing single serotonergic dorsal raphe (DRN), noradrenergic locus coeruleus (LC) and dopaminergic ventral tegmental (VTA) and zona compacta (ZC) neurons, and cerebellar Purkinje neurons (PC) in urethane anesthetized rats in vivo. Cocaine (0.0625-4 mg/kg) predominantly inhibited all of the central monoaminergic neurons and predominantly activated cerebellar Purkinje neurons. Cocaine (1 mg/kg, IV) failed to potentiate the inhibitory effects of LC stimulation on PC neurons. The temporal effects of intravenous cocaine on arterial pressure (i.e., pressor response) were not directly correlated with the effects on neurons. Cocaine did not decrease the amplitude or slope of neuron action potentials, and the effects of cocaine on firing rate were not shared by similar doses of procaine. Reserpine pretreatment (10 mg/kg, IP) attenuated the effects of cocaine (1 mg/kg, IV) on DRN, LC, and PC neurons. Specific adrenoceptor antagonists antagonized the inhibitory effects of cocaine on LC (piperoxane, yohimbine) and VTA (haloperidol) neurons. These results suggest that the central effects of cocaine on presynaptic monoaminergic neurons may in part be mediated by augmented monoamine neurotransmission at autoreceptors and that the effects of cocaine on postsynaptic target cells (PC) may be more complex, requiring the analysis of both pre- and postsynaptic elements.

Animals↗
PubMed1987

Electrophysiological actions of cocaine on noradrenergic neurons in rat locus ceruleus.

Extracellular microelectrode experiments were conducted to study the effects of cocaine HCl on the activity of spontaneously firing single locus ceruleus (LC) noradrenergic neurons in vivo. The responses of single identified noradrenergic LC neurons to the systemic (i.v.) administration of cocaine were observed over a wide range of doses (0.0625-2.0 mg/kg). The spontaneous activity of all LC neurons receiving doses greater than the threshold dose (0.0625 mg/kg) was inhibited in a dose-dependent manner. The local anesthetics, procaine and mepivacaine, did not affect LC neuronal activity, action potential amplitude or slope. The inhibitory effects of cocaine on spontaneous LC neuron activity was reversed by the subsequent i.v. administration of the specific alpha-2 adrenoceptor antagonist, piperoxone, but not the opiate receptor antagonist, naloxone. Pretreatment with another alpha-2 adrenoceptor antagonist, yohimbine (5 mg/kg i.p.), attenuated significantly the inhibition of spontaneous LC activity elicited by i.v. cocaine. Intravenous cocaine produced a brief increase in mean arterial pressure which did not appear to be correlated with the more sustained inhibition of LC neurons. Reserpine pretreatment (10 mg/kg i.p.) attenuated significantly the inhibitory effects of cocaine on LC activity. These results suggest that the inhibition of spontaneous LC neuron activity by i.v. cocaine is most likely mediated by an augmented action of catecholamines at central alpha-2 adrenoceptors and not by the local anesthetic effects of cocaine.

Action Potentials↗
PubMed1986

Electrophysiological effects of cocaine on central monoaminergic neurons.

The electrical activity of three different single, identified, spontaneously firing central neurons was monitored by extracellular microelectrodes. Intravenous cocaine administration (0.25-2 mg/kg) elicited an activation of cerebellar Purkinje neurons (PN) and an inhibition of serotonergic dorsal raphe (DRN) and noradrenergic locus coeruleus (LC) neurons. These effects were not temporally correlated with the increase in mean arterial pressure elicited by the intravenous administration of cocaine. In addition, the administration of procaine, a structurally related local anesthetic, did not significantly affect any of the three central neurons studied. Our results suggest that cocaine has potent effects on the activity of DRN, LC and PN neurons, which are not directly related to its cardiovascular or local anesthetic actions.

Animals↗
PubMed1986

Cardiovascular effects of perfusion of the rostral rat hypothalamus with clonidine: differential interactions with prazosin and yohimbine.

The present studies examined the role of alpha 1- versus alpha 2-adrenoceptors in the cardiovascular effects of clonidine administered into the anterior hypothalamic/pre-optic (AH/PO) region of the forebrain by the push-pull perfusion technique. Push-pull cannulas were placed bilaterally into the AH/PO region of anesthetized, paralyzed and ventilated rats. Perfusion of this area with artificial CSF (0.015 ml/min), yohimbine (5 or 50 microM) for 30 min did not affect mean arterial blood pressure or heart rate. Perfusion of the AH/PO region with clonidine (0.55-5.50 mM) resulted in a concentration-dependent reduction of mean arterial pressure and heart rate. The hypotensive effects of clonidine were found to be greater than the bradycardic effects, when expressed as a percent of pre-infusion baseline values. Co-perfusion with yohimbine (5, 50 microM) significantly attenuated the hypotensive, but not the bradycardic, effects of a single concentration (1.75 mM) of clonidine; this selective antagonism of the hypotensive effect of clonidine by yohimbine was concentration dependent. In contrast to yohimbine, co-perfusion with 5 microM prazosin did not significantly affect either the clonidine-induced hypotension or bradycardia. Co-perfusion with the higher concentration (50 microM) of prazosin significantly reversed the bradycardic, but not the hypotensive, effects of 1.75 mM clonidine. These results suggest that AH/PO clonidine perfusion depresses both mean arterial pressure and heart rate, and that the clonidine-induced hypotension is due to alpha 2-adrenoceptor activation, while the clonidine-induced bradycardia is due to alpha 1-adrenoceptor activation.

Animals↗
PubMed1986

Effects of cocaine on the electrical activity of single noradrenergic neurons from locus coeruleus.

The effects of intravenous (i.v.) cocaine HCl on single identified spontaneously firing noradrenergic neurons in the nucleus locus coeruleus (LC) were studied in rats in vivo. Cocaine (0.25-1 mg/kg) produced inhibition of spontaneously firing LC neurons, which was reversed by the administration of the selective alpha 2-adrenoceptor antagonist, piperoxane (250 micrograms/kg, i.v.). Procaine, a local anesthetic that is structurally related to cocaine, did not inhibit LC neurons in doses up to 4 mg/kg, i.v. These results suggest that cocaine in low doses has significant central sympathomimetic effects at the single noradrenergic neuron level and that the inhibition of spontaneous activity may be mediated by alpha 2-adrenoceptors. Our results also indicate that cocaine in pharmacologically relevant doses, can significantly affect central alpha 2-adrenoceptor regulatory processes.

Animals↗
PubMed1985

Cardiovascular effects of centrally perfused clonidine.

Earlier work has indicated that the systemic cardiovascular actions of clonidine might be mediated by caudal brainstem centers, especially the nucleus of the solitary tract (NTS). This study sought to define the mode of clonidine action on the NTS more explicitly using the technique of push-pull perfusion on urethane-anesthetized rats. The NTS of stereotaxically mounted subjects was unilaterally perfused with an artificial cerebrospinal fluid at 25 microliter/min. Clonidine was added to the medium at concentrations of 5 to 500 microM, without interruption of flow, for test periods of 10 min. Systemic drug actions were expressed in terms of mean arterial pressure (MAP) and heart rate (HR), both of which were recorded continuously throughout the experiment. Decreases occurred in both MAP and HR following clonidine perfusion at all concentrations. However, the dose-effect relationship for the blood pressure response was dependent to some extent on control pressure. When this was considered as a variable, the drug-induced pressure effects were significantly dose-dependent. Control HR values were more stable than pressure and dose-related decreases following clonidine administration were highly significant. The clonidine concentrations investigated here were considerably lower than those previously studied by microinjection. The observed dose-related depression of MAP and HR under basal conditions may be related to specific alpha 2-adrenergic receptor activation of the NTS.

Animals↗
PubMedDate not supplied

Prenatal haloperidol reduces the number of active midbrain dopamine neurons in rat offspring.

The dopamine (DA) receptor antagonist, haloperidol (HAL, 1.25 or 5 mg/kg), or vehicle, dimethyl sulfoxide (DMSO), was administered (SC) daily to pregnant Sprague-Dawley dams from gestational day (GD) 8 to GD 20. The average body weight of 2-week-old male offspring was significantly lower in all of the HAL-treated groups relative to controls. In extracellular electrophysiological studies, the male 2-week-old offspring from all HAL treatment groups were found to have significantly reduced average numbers of spontaneously active midbrain dopamine (DA)-containing neurons in both the substantia nigra (A9) and the ventral tegmental area (A10) relative to controls. In DA neurons classified as bursting neurons, HAL exposure (5 mg/kg) caused a significantly increased level of burst activity in A10 but not A9 DA neurons relative to controls. For both the A9 and A10 regions, the proportion of DA neurons classified as bursting or nonbursting was unaffected by HAL treatment. These results suggest that prenatal HAL exposure influences the development of midbrain DA neurons.

Animals↗
PubMedDate not supplied

Effects of chronic low-level oral lead exposure on prepulse inhibition of acoustic startle in the rat.

Previous work has suggested that the behavioral effects of chronic low-level lead exposure on fixed interval (FI) operant behavior result from enhanced dopaminergic neurotransmission in the nucleus accumbens (Cory-Slechta et al., J Pharmacol Exp Ther 286: 794-805, 1998). The present studies were designed to further characterize the effects of chronic low-level oral lead exposure on another behavior that is modulated by dopaminergic neurotransmission in the nucleus accumbens. In these studies acoustic startle and the prepulse inhibition (PPI) of startle were studied in rats following chronic low-level oral lead exposure. Weanling male rats were treated for 5-6 weeks with lead via drinking water (250 ppm lead acetate; controls drank 250 ppm sodium acetate). Acoustic startle reactivity (95, 105, and 115 dB noise bursts) and PPI (prepulses of 1-8 dB over the 70-dB background) of startle were tested following lead exposure. Lead exposure did not affect body weight. Lead exposure also did not significantly affect baseline [i.e., no prepulse inhibition (NO-PPI)] acoustic startle as measured by 1) startle amplitude on the first startle trial (105 dB), 2) the average startle amplitude for the first ten trials (105 dB), or 3) the average startle amplitude for the NO-PPI trials during PPI testing (95, 105, and 115 dB). Lead exposure also did not affect the latency to onset for the startle response. In contrast, for both the 105 dB and 115 dB acoustic startle stimuli, chronic low-level oral lead exposure significantly attenuated the capacity of an acoustic prepulse to reduce the startle response. This effect was present whether the data were presented and analyzed as raw change from baseline or as the percentage of baseline startle. Given the strong link between the modulation of PPI and dopaminergic neurotransmission in the nucleus accumbens, the present data support the hypothesis that chronic low-level oral lead exposure facilitates dopamine neurotransmission in the nucleus accumbens.

Acoustic Stimulation↗