Neurochemical and behavioral factors in the development of tolerance to anorectics.

Four tests, with 60 male Sprague-Dawley rats, investigated tolerance and cross-tolerance among several anorectic drugs. In the 1st test, Ss given milk shortly after intraperitoneal injection of 3 mg/kg dextroamphetamine sulfate (controls) developed tolerance to amphetamine anorexia, but Ss given milk when amphetamine's anorectic effects had worn off (experimental Ss) did not develop tolerance in spite of equal drug exposure. In the 2nd test, controls were tolerant to 2 mg/kg apomorphine HCL, a drug with a neurochemical action related to amphetamine. No tolerance to 2 mg/kg apomorphine was shown by experimental Ss. Both groups were tolerant to 1.25 mg/kg apomorphine. The final test replicated part of the 1st test, demonstrating that the control group was tolerant to amphetamine but the experimental group was not. In addition, neither group was tolerant to anorexia produced by 5 mg/kg fenfluramine, a drug whose action is neurochemically different from amphetamine and apomorphine. It appears that both learning and specific neurochemical mechanisms are involved in the development of tolerance to anorectic drugs. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- or D-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9 micrograms/4 microliters/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) and D-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at -70 degrees C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of > 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75-90% depleted) rats were found to rotate on D-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively on D-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not with D-amphetamine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of different doses of apomorphine on the glutamate decarboxylase activity of the substantia nigra and the medial basal hypothalamus

The activity of gamma-aminobutyric acid (GABA) synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) was assayed in the rat substantia nigra (SN) and medial basal hypothalamus (MBH) following systemic injection of different doses of the dopamine receptor agonist apomorphine. In SN, the highest dose of apomorphine (1000 micrograms/kg) causes an increase of the GAD activity whilst an opposite effect is observed with the lowest dose (35 micrograms/kg). Results obtained in SN are in accordance with previous neurochemical and behavioural data suggesting an opposite action of high (500 micrograms/kg) and low doses (100 micrograms/kg) of apomorphine in nigro-striatal system, probably due to the existence of two classes of dopamine receptors, i.e. classical postsynaptic dopamine receptors and presynaptic inhibitory dopamine autoreceptors. In MBH, the evidence for similar effects of low and high doses of apomorphine (the decrease of GAD activity) may suggest that, as already reported, at this level only one class of dopamine receptors is present.     

Effects of different doses of apomorphine on GAD activity in rat substantia nigra

The effects of different doses of the dopamine (DA) receptor agonist apomorphine on the activity of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase (GAD, EC 4.1.1.15) were investigated in rat substantia nigra in comparison with haloperidol and sulpiride, two DA receptor blocking agents. Results obtained show that low doses (10,35 microgram/kg, s.c.) of apomorphine induce a decrease in nigral GAD activity whilst an opposite effect is observed with the highest dose (1000 microgram/kg, s.c.). No significant change is observed following injection of the intermediate doses (100 and 500 microgram/kg, s.c.). Moreover, sulpiride at the dose used (2 mg/kg, i.p.) induces an increase in GAD activity whilst no effect follows systemic injection of the same dose of haloperidol. The results are discussed in light of recent neurochemical and behavioral data.     

Psychopathology of posttraumatic epilepsy in the light of personal clinical observation

The influence of apomorphine, chloral hydrate, haloperidol, morphine, oxotremorine, pargyline, probenecid and promethazine on DOPAC and HVA levels was studied in the substantia nigra (including the ventral tegmental dopaminergic regions) and corpus striatum of the rat brain. The time--effect curves of changes in HVA levels after pretreatment with apomorphine, haloperidol, morphine, oxotremorine or promethazine are presented. The time--effect curves for the substantia nigra showed an initial rapid HVA rise, which was not observed in the corpus striatum. Promethazine treatment caused a small but significant HVA rise in the substantia nigra only. Chloral hydrate, morphine and oxotremorine induced a similar percentage increase in DOPAC and HVA levels in the substantia nigra as well as in the corpus striatum. Haloperidol, however, caused a small percentage change in the metabolite levels in the substantia nigra when compared to the pronounced rise seen in the corpus striatum. The apomorphine-induced HVA decrease observed in both structures provides evidence for the presence of a dopaminergic receptor in the substantia nigra.     

Stereotyped behavior and diabetes mellitus in rats: Reduced behavioral effects of amphetamine and apomorphine and reduced in vivo brain binding of [–3H]spiroperidol.

In 4 experiments, male Sprague-Dawley rats made diabetic by an intravenous injection of streptozotocin (65 mg/kg) showed decreased stereotyped behaviors following subcutaneous (sc) administration of apomorphine HCL (1 mg/kg) or dextro-amphetamine sulfate (3 mg/kg). Spontaneous activity in an open field was lower in diabetics than in controls, but a low dose (25 μg/kg, sc) of apomorphine produced equivalent fractional decreases in activity in both groups. In vivo accumulation of amphetamine and apomorphine was generally similar in both groups: Reduced tissue access did not appear to be responsible for the decreased behavioral effects of these agents. The in vivo accumulation of spiroperidol in several brain regions was generally less in diabetics than in controls. Data are discussed in terms of altered catecholamine biochemistry and behavior in diabetics. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Automated measurement of stereotypic behavior in rats.

Compared an animal activity monitoring system in which 2 of the motor variables measured constitute an index of stereotyped behaviors with a standard visual stereotypy rating scale following the administration of apomorphine or amphetamine. The automated measure "number of stereotypies" failed to show a significant dose-response effect with amphetamine, and the measure "stereotypy time" was less sensitive to the effects of apomorphine. The 2 measures, however, significantly correlated with the visual scales and, in combination, revealed the ongoing stereotypic effects of the drugs over time and thus eliminated confounding variables, such as experimenter bias, commonly associated with visual rating techniques. (6 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of thalamic and hypothalamic somatosensory evoked potentials by stimulation of substantia nigra and its modification by morphine and methotrimeprazine (levomepromazine)

A brief electrical stimulation of the substantia nigra induced a marked and long lasting inhibition of the somatosensory evoked potentials recorded from the centrum medianum of the thalamus (CM) and posterior hypothalamic area (PHA) following sciatic stimulation in unanesthetized rabbits. The nigral inhibitory effect on CM was prolonged by the administration of morphine (4 mg/kg i.v.) but not influenced by that of methotrimeprazine (2-4 mg/kg i.v.). In contrast, the nigral inhibitory effect on PHA was enhanced by the injection of methotrimeprazine (2 mg/kg i.v.), but not changed by that of morphine (4 mg/kg i.v.). These results indicate that the inhibitory system originating from the substantia nigra operates on the somatosensory transmissions from the peripheral nerve to the thalamus and hypothalamus, and that morphine or methotrimeprazine in small doses induced a selective potentiation of the nigral inhibitory influence on the thalamus or hypothalamus, respectively.     

Hypotheses on the role of cytokines in peptic ulcer disease

BACKGROUND: A novel gastric pentadecapeptide, BPC 157, has been shown to attenuate different lesions (i.e., gastrointestinal tract, liver, pancreas, somatosensory neurons). This suggests an interaction with the dopamine system. When used alone, BPC 157 does not affect gross behavior or induce stereotypy. METHODS: We first investigated the effect of pentadecapeptide BPC 157 on stereotypy and acoustic startle response in rats, given as either a prophylactic (10 micrograms/kg i.p.) or therapeutic (10 ng/kg i.p.) regimen, with the dopamine indirect agonist amphetamine (10 mg/kg i.p.). RESULTS: There was a marked attenuation of stereotypic behavior and acoustic startle response. When the medication was given at the time of maximum amphetamine-induced excitability, there was a reversal of this behavior. A further focus was on the effect of this pentadecapeptide on increased climbing behavior in mice pretreated with the dopamine antagonist haloperidol (5.0 mg/kg i.p.), and subsequently treated with amphetamine (20 mg/kg i.p. challenge 1, 2, 4, and 10 days after haloperidol pretreatment). This protocol is usually used for the study of behavioral supersensitivity to the amphetamine stimulating effect. CONCLUSIONS: An almost complete reversal was noted when pentadecapeptide was coadministered with haloperidol. Together, these data provide compelling evidence for the interaction of pentadecapeptide BPC 157 with the dopamine system.     

Blood pressure and heart rate response to apomorphine in urethane anesthetized rats

The mechanisms involved in the hypotensive effect of apomorphine were studied in urethane anesthetized rats. The intravenous injection of apomorphine (0.01-0.75 mg/kg) produced a dose dependent fall in mean blood pressure. At the higher doses used (0.5-0.75 mg/kg) a marked bradycardia accompanied the hypotensive effect. These cardiovascular effects were prevented by pretreating the animals with pimozide (0.01-0.1 mg/kg). Low doses of haloperidol (0.03-0.3 mg/kg) did not antagonize the hypotensive action of apomorphine. Higher doses of haloperidol (1-3 mg/kg) reduced markedly the mean blood pressure. Atropine (1 mg/kg) partially antagonized the decrease in mean blood pressure induced by apomorphine and prevented completely the bradycardia. Hexamethonium (10 mg/kg) reduced the mean blood pressure and when apomorphine was administered, a residual hypotensive effect and no bradycardia was observed. It is concluded that the cardiovascular actions of apomorphine are central in origin and mainly due to the stimulation of a dopamine receptor. A probable peripheral effect could not be discarded.     

Case of oculocraniosomatic neuromuscular disease associated with parkinsonism with special reference to catecholamine metabolism

Three groups of rats (A, B, C) were trained in a T-maze discriminate between drug-and control solution-induced internal discriminative stimuli. The drugs used to induce discriminative stimuli were: delta 9-THC, 5.0 mg/kg (Group A); ethanol, 1.2 g/kg (Group B), and amphetamine, 1.0 mg/kg(Group C). After discrimination acquisition several drugs were tested for generalization in each group. Group A was tested with delta 8-THC, CBD, CBN, ethanol, pentobarbital,chlorpromazine, amphetamine, and apomorphine; only delta8-THC and CBN induced delta9-THC-like responses. Group B was tested with delta 9-THC, delta 8-THC, CBD, CBN, pentobarbital, and amphetamine; pentobarbital induced ethanol-like response. Group C was tested with delta 9-THC, apomorphine, and ethanol; delta 9-THC and apomorphine elicited amphetamine-like responses.     

Hypochord, an enigmatic embryonic structure: study of the axolotl embryo

Age-dependent alterations in behavioral and neuronal functioning were assessed in young (2-3 month), middle-aged (12 month), and aged (24 month) Fischer 344 rats treated with the indirect dopamine agonist amphetamine (2.25 or 5 mg/kg), the D1 agonist SKF 38393 (7.5, 15, 30 mg/kg), or the D2 agonist quinpirole (0.3, 1.0, 3.0 mg/kg). Drug-induced changes in activity and stereotypy were measured during a 90-min testing session, with Fos immunohistochemistry being used to assess the neuronal response to dopamine agonist treatment. As expected, aged rats given amphetamine (5 mg/kg) had fewer activity counts and higher stereotypy scores than young rats. Middle-aged rats also had fewer activity counts but were similar in stereotypy scores to young rats. Amphetamine also induced different patterns of Fos immunoreactivity in the neostriatum and nucleus accumbens of young and aged rats, as Fos expression in aged rats exhibited a distinctive dorsal to ventral pattern of decline. In general, SKF 38393 had few age-related actions, although aged rats did show a slight relative increase in stereotypy. In contrast, the D2 agonist quinpirole substantially enhanced the motor activity and Fos expression of young rats, while only modestly affecting aged rats. Hence, these results suggest that the D2 receptor is more vulnerable to the effects of aging than the D1 receptor.     

Effects of d- versus l-amphetamine, food deprivation, and current intensity on self-stimulation of the lateral hypothalamus, substantia nigra, & medial frontal cortex of the rat.

Studied intracranial self-stimulation (ICSS) in 18 adult Sprague-Dawley rats with chronically implanted lateral hypothalamic, substantia nigra, or medial frontal cortex bipolar electrodes. A comparison of the effects of dextro- and levoamphetamine on ICSS response rate indicated that the dextro isomer had a greater facilitatory effect than the levo isomer at lateral hypothalamic and substantia nigra electrode sites but that neither isomer significantly affected medial frontal cortex ICSS. Dextroamphetamine resulted in a dose-related increase in motor activity, but the same doses of the levo isomer resulted in decreased motor activity. Only lateral hypothalamic ICSS response rates increased significantly in response to food deprivation. Increases in current intensity above the level used for amphetamine and food-deprivation testing facilitated lateral hypothalamic and substantia nigra ICSS response rates. The responsiveness of ICSS at each electrode site appeared to be correlated with the fiber- and cell-body densities of catecholaminergic systems in the brain. (42 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of neonatal dopamine depletion on sensory inhibition in the rat

Central dopamine systems appear to play an important role in sensory information processing. In particular, the filtering (or gating) of repetitive auditory stimuli is modulated by pharmacological manipulations that affect dopaminergic neurotransmission. The present study further addressed the role of dopamine in auditory gating. Three-day-old male Sprague-Dawley rats, pretreated with desipramine, received intracisternal injections of 6-hydroxydopamine (6-OHDA; 75 micrograms in 10 microliters) or the vehicle. At 4 months of age the rats were implanted for evoked potential recording and auditory gating was assessed using a paired click paradigm. Neonatally administered 6-OHDA did not alter gating in the adult rats. However, unlike for the control group, systemic amphetamine (1.83 mg/kg, IP) failed to disrupt gating in the treated rats. Apomorphine (1.0 mg/kg, SC) disrupted gating in both groups. Neonatal 6-OHDA treatment caused significant reductions in dopamine levels in the striatum, nucleus accumbens, and substantia nigra/ventral tegmental regions. There was an inverse relationship between substantia nigra/ ventral tegmental area dopamine levels and auditory gating. Overall, the results suggest that amphetamine-induced auditory gating loss requires presynaptic dopamine release, but that the deficiency occurs through postsynaptic dopamine receptor activation.     

Effects of the NMDA-antagonist, MK-801, on stress-induced alterations of dopamine dependent behavior

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day x 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.     

Sensitization of amphetamine-induced stereotyped behaviors during the acute response

The quantitative and qualitative features of the behavioral response to amphetamine-like stimulants in rats can be dissociated from the dopamine response. This dissociation is particularly evident in the temporal profiles of the extracellular dopamine and stereotypy responses to higher doses of amphetamine. One possible mechanism contributing to this temporal dissociation is that during the acute response to amphetamine, dopamine receptor mechanisms are enhanced such that stereotyped behaviors can be supported by synaptic concentrations of dopamine which are not sufficient to initiate these behaviors. To further explore the dynamics of stimulant sensitivity during the acute response, we examined the behavioral and extracellular dopamine responses to a low, nonstereotypy-producing dose of amphetamine (0.5 mg/kg) at various times after an acute, priming injection of 4.0 mg/kg when stereotypies had subsided and extracellular dopamine was approaching predrug baseline levels. The low-dose challenge produced intense stereotypies although the regional dopamine responses were not significantly different from control animals. Blockade of the expression of stereotypies during the priming response by the D2 antagonist haloperidol or the D1 antagonist SCH 23390 prevented the expression of an enhanced stereotypy response to the challenge injection. Our results suggest that an exposure to amphetamine results in a rapid sensitization of the stereotypy response which does not involve changes in the extracellular dopamine response but requires activation of dopamine receptors. Such a mechanism may be significantly implicated during binge patterns of stimulant abuse and may also play a role in the sensitization associated with repeated amphetamine administration.     

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.     

The elastic cartilage in the normal rat epiglottis. I. Fine structure

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling. The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus-nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.     

The effects of limbic lesions on locomotion and stereotypy elicited by dopamine agonists in the rat

The purpose of this experiment was to investigate the functional contributions of various limbic structures to locomotion and stereotypy induced by dopaminergic drugs. Female rats were randomly assigned to one of 5 groups (n = 10-14 rats/group) that received either a lesion of the hippocampus (colchicine + kainic acid), basolateral amygdala (quinolinic acid), frontal cortex (aspiration), nucleus accumbens (ibotenic acid), or served as unoperated controls. Beginning at least 2 weeks following surgery locomotion (measured as photocell beam breaks) elicited by D-amphetamine (0.0, 0.32, 1.0 and 3.2 mg/kg), SKF 82958 (0.0, 0.04, 0.08 and 0.16 mg/kg) or quinpirole (0.0, 0.25, 0.1 and 0.5 mg/kg) was determined. In agreement with previous results rats with hippocampal lesions were hyperactive in response to amphetamine. In comparison to these changes in drug-induced locomotion, lesions of the basolateral amygdala, and frontal cortex had only minor effects on drug-induced locomotion. Lesions of the nucleus accumbens produced consistent hyperactivity that was suppressed by doses of amphetamine or quinpirole that elicited behavioral stereotypy. These results provide evidence suggesting that, in comparison to other limbic structures that have substantial inputs to the nucleus accumbens, the hippocampus play a relatively prominent role in the modulation of drug-induced locomotion.     

The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain

The importance of extrapyramidal and mesolimbic function for circling behaviour was investigated by placing 6-hydroxydopamine (6-OHDA) and electrolesions in the cell bodies, axons and terminals of each system. Circling behaviour was weak when 6-OHDA was placed at the centre of the substantia nigra (SN), but the characteristic contralateral/ipsilateral turning to apomorphine/amphetamine were recorded. Circling was more marked when 6-OHDA was placed anterior to the SN but was generally absent following injections posterior to the SN. However, 6-OHDA placed in the medial forebrain bundle in the lateral hypothalamus resulted in intense contralateral/ipsilateral turning to apomorphine/amphetamine. Generally, the intensity of circling responses was related to the degree of striatal dopamine (DA) depletion but the more effective lesions also caused reductions in mesolimbic DA content. However, circling was not observed following any 6-OHDA injection into the mesolimbic DA system and it is concluded that mesolimbic DA function is not essential for the initiation of circling. In contrast to the 6-OHDA lesions, rats circled ipsilateral to both apomorphine and amphetamine when the SN was damaged by electrocoagulation to cause marked depletion of striatal dopamine. Lesser depletions of striatal dopamine after electrocoagulation in different regions of the medial forebrain bundle were associated with a lower intensity of ipsilateral circling to both drugs. In general, the differences between 6-OHDA and electrolesions could not be explained by additional damage to ascending noradrenaline or 5-hydroxytryptamine pathways. Lower doses of apomorphine were effective in the 6-OHDA circling rats, and the ipsilateral striatum of such rats was more sensitive to directly applied DA. Higher doses of apomorphine were required to produce circling after chronic electrolesions which rendered the ipsilateral striatum insensitive to DA. The contralateral circling to apomorphine after 6-OHDA lesions was abolished by chronic but not by acute electrolesion of the SN. It is suggested that electrolesions of the SN cause different effects to 6-OHDA because they destroy neuronal pathways in addition to the dopaminergic nigrostriatal tract. These appear to be required for the expression of circling behaviour caused by stimulation of the denervated striatum. Whereas 6-OHDA lesions result in super-sensitivity of the denervated strital DA receptors, electrolesions may cause a hypo-sensitivity of the same receptor sites.