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PubMed1985

Relative effectiveness of pimozide, haloperidol and trifluoperazine on self-stimulation rate-intensity functions.

Rats were trained to lever press for 60 Hz sine wave stimulation of the medial forebrain bundle (MFB) at the level of the lateral hypothalamus. Rate intensity functions were determined by stepping down the current intensity by 0.05 log10 units every five min. Haloperidol shifted the function approximately one step to the right at 0.08 mg/kg, with lower doses producing no effect. Pimozide shifted the curve in a dose-dependent manner over the range of 0.06 to 0.24 mg/kg; 0.12 mg/kg produced an approximate one-step shift. Trifluoperazine also produced dose related shifts to the right over the range of 0.08 to 0.32 mg/kg; this agent, unlike the others, appeared to shift the curve down as well as to the right. Less than a one-step shift was produced by 0.08 mg/kg; more than a one-step shift was produced by 0.16 mg/kg. On a molar basis, the order of potency for displacing the curves to the right was haloperidol, pimozide and trifluoperazine. While this order of potency is not predicted from simple in vitro binding affinities for the D2 receptor, this may be due to differences in the penetration of these agents to central D2 receptors in vivo.

Animals↗
PubMed1976

Decreased intracranial self-stimulation after neuroleptics or 6-hydroxydopamine: evidence for mediation by motor deficits rather than by reduced reward.

Rats were implanted with electrodes in the lateral hypothalamus, put on a 22-h food deprivation schedule and trained to bar-press for ICS and for food on a CRF schedule. Haloperidol (0.08 mg/kg) and pimozide (0.22 mg/kg) significantly decreased responding for both reinforces, although responding for ICS was decreased more than it was for food. The same doses of these drugs did not decrease food consumption of a 15-min ad libitum test after 22-h of food deprivation, suggesting that the decreased bar-pressing for food was not the result of anorexia or reduced motivation for food. When similar rates of responding for ICS and for food were obtained on a V1 60 schedule, haloperidol (0.1 mg/kg) reduced responding for food and ICS to a similar extent. Thus, when baseline rate is controlled for, neuroleptics do not selectively reduce responding for ICS. In addition, examination of cumulative response records revealed that rather than producing an extinction curve, as would be predicted if neuroleptics reduced the rewarding properties of ICS, haloperidol produced a uniform decrease in the rate of responding throughout the experimental session. Similar results were obtained with intraventricular 6-hydroxydopamine (6-OHDA) injections. While these experiments do not exclude the possibility that dopaminergic (DA) systems participate in some central reinforcement mechanisms, they suggest that neuroleptics and 6-OHDA decrease responding for food or ICS primarily by impairing the function of DA systems critically involved in the initiation or maintenance of operant behaviour rather than by interfering with reward.

Animals↗
PubMed1994

Proposed pathways for vocal self-stimulation: met-enkephalinergic projections linking the midbrain vocal nucleus, auditory-responsive thalamic regions and neurosecretory hypothalamus.

In this study, we have investigated the neuroanatomical pathways that may underlie the influence of a female bird's vocal behavior upon her own reproductive endocrine response. We traced the ascending efferent projections of the midbrain vocal control nucleus, the intercollicularis (ICo), using an anterograde tracer, PHAL, delivered by iontophoretic application. We found labelled terminal fields in the anterior regions of the hypothalamus that contained luteinizing hormone releasing hormone- (LHRH) immunoreactive neurons. We injected into the LHRH-rich anterior medial hypothalamus (AM) the retrograde tracer, fluoro-gold, to verify the results of PHAL anterograde tracing and examine whether retrogradely labelled neurons in the ICo can be stained with met-enkephalin antiserum by the immunohistochemical method. Of the retrogradely labelled neurons in the medial division of ICo (mICo), between 5% and 15% were found to be met-enkephalin-immunoreactive positive perikarya. Our data suggest that axonal projections into the anterior medial hypothalamus may arise in part from enkephalin-immunoreactive neurons in the medial ICo. The mICo neurons distributed along the medial border of the midbrain auditory nucleus give rise to projections into the posterior medial hypothalamus (PMH) via synapses within the shell region of thalamic auditory nucleus, ovoidalis (Ov). We conclude that in the ring dove, the medial division of the vocal control nucleus, by virtue of its connection with the auditory thalamus and neurosecretory hypothalamus, is in a position to exert influence on endocrine response partly through enkephalinergic systems. Implications of similar connections in other species are discussed.

Animals↗
PubMed1980

Chronic self-stimulation of the medial posterior inferior thalamus for the alleviation of deafferentation pain.

Since current techniques yield uncertain results on deafferentation pain, chronic brain stimulation may presumably be a valuable alternative method, without deterrent side-effects. Disappointing results with stimulation of the somato-sensory structures prompted the selection of the medial posterior inferior thalamus and adjacent brain stem for chronic stimulation in pain states of central origin. Six such cases are reported. Abolition of the hyperpathia and marked reduction in the deep background pain was achieved in 2 cases, and disappearance of the hyperpathia and moderate reduction in the deep pain was obtained in another 2, but none had complete alleviation of pain. The follow-up time ranged between 6 and 42 months. Reversal of analgesia by naloxone was not observed. Acute experimentally-induced pain was not modified by stimulation.

Analgesia↗
PubMed2004

In rats, acute morphine dependence results in antagonist-induced response suppression of intracranial self-stimulation.

RATIONALE: Lower (0.001-1.0 mg/kg) doses of the opioid antagonist naltrexone produce few behavioral effects in otherwise drug-free rats responding for ICSS, but reduce response rates by up to 75% after a single dose of morphine. OBJECTIVES: The present study represents an effort to verify that other opioid antagonists produce this acute opioid dependence effect, and to characterize their relative pharmacological profiles. METHODS: We implanted bipolar electrodes in the lateral hypothalamus of adult male rats, and then trained them to lever-press on an "autotitration" ICSS schedule, where responding on a "reset" lever allows the rat to control the frequency of stimulation; performance stabilized at approximately 1.5 responses/s. RESULTS: During twice-weekly test sessions, cumulative doses of five of seven opioid antagonists produced significant response rate decreases (30-80%) in saline-pretreated rats; nalorphine (ED25=15.6 mg/kg)> naltrexone (ED25=13.1 mg/kg)>naloxone (ED25=7.3 mg/kg)>levallorphan (ED25=13.96 mg/kg)>(-)cyclazocine (ED25=0.028 mg/kg). A single MOR pretreatment (10 mg/kg, 4 h) significantly enhanced the rate-decreasing effects of six of the seven agonists tested; by 10-fold (-) cyclazocine>13-fold (nalorphine)>93-fold (levallorphan)>972-fold (naloxone)>2190-fold (naltrexone). The pure non-selective antagonist diprenorphine potently decreased rates after MOR pretreatment (ED25= 0.01 mg/kg), but did not after saline pretreatment. The mixed opioid agonist-antagonist drug nalbuphine (1.0-30 mg/kg) did not affect responding after either saline or MOR. CONCLUSIONS: Antagonists with a high affinity for, and a lack of intrinsic activity at, the micro-opioid receptor precipitate the greatest behavioral changes in rats acutely dependent on MOR.

Acute Disease↗
PubMed1986

Quinine tolerance during self-stimulation in cats.

Thirsty cats, offered a choice between distilled water and quinine solution, preferred the latter to distilled water and accepted quinine concentrations greater than those they accepted in control sessions when drinking quinine solution was rewarded by hypothalamic stimulation, whereas drinking distilled water was not. When the same stimulation rewarded drinking distilled water only, the cats switched to distilled water and refused quinine solutions at concentrations even less than those previously accepted in control sessions. It was concluded that drinking quinine solution was an instrumental response which secured the desirable hypothalamic stimulation.

Animals↗
PubMed1997

Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold?

Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in suprathreshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second "reset" lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in "reward value". In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days--parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of "reward value" that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between "resets". Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task.

Animals↗
PubMed1996

Physiological parameters associated with the performance of a distracting task and genital self-stimulation in women with complete spinal cord injuries.

OBJECTIVE: To compare the physiological sexual responses of women with complete spinal cord injuries (SCI) with those of able-bodied women. DESIGN: Controlled laboratory-based analysis of responses to a distracting task coupled with manual genital stimulation versus masturbation. SETTING: The sexual physiology laboratory at our free-standing rehabilitation hospital. PARTICIPANTS: A volunteer sample of 10 women with complete SCI along with 10 able-bodied women, matched for age and educational status. INTERVENTIONS: A 78-minute protocol using 6-minute baselines alternating with 12-minute testing conditions. DEPENDENT-VARIABLES: Vaginal pulse amplitude, subjective arousal, heart rate, respiratory rate, and blood pressure. RESULTS: Subjective sexual arousal increased in able-bodied women with manual genital stimulation in conjunction with performance of a distracting task and was further augmented by removal of the distracting task and continuing with masturbation. In contrast, complete SCI subjects did not demonstrate increased subjective arousal with performance of the distracting task in conjunction with manual genital stimulation; however, they did evidence significant increases in arousal when the distracting task was eliminated. CONCLUSIONS: Genital responses tended to parallel subjective responses in able-bodied women; however, women with SCI revealed nonsignificant changes in genital responses throughout the treatment protocol. It is hypothesized that the genital and subjective responses of able-bodied subjects reflect the additive components of reflex and then psychogenic sexual arousal. Furthermore, the lack of responsivity in the SCI subjects was thought to be related to compromised upper extremity function in the majority of our subjects. Further work is necessary to validate these hypotheses.

Adult↗
PubMed1996

Classical conditioning of electrical self-stimulation of ventral tegmental area to brief visual stimuli in rats.

Two groups of rats with bipolar electrodes implanted unilaterally into the left ventral tegmental area were trained to lever-press for the response contingent electrical stimulation. After preliminary lever-press training, two types of daily sessions were held on 10 consecutive days: type T+, current intensity set at the Threshold level and each response was accompanied by the visual signal (stimulus lights above the lever briefly went off): and type ST-, current set at the Sub Threshold level and no visual stimuli. On day 11, combination of the subthreshold current intensities and stimulus lights previously associated with the threshold stimulation (session type ST+) resulted in a significantly elevated response rates compared to the performance under the subthreshold current without visual stimuli (session type ST-). The extinction and recovery of this phenomenon are also demonstrated.

Animals↗