Decrease In Self-stimulation Research Articles

SCH 23390 decreases self-stimulation of the medial prefrontal cortex in the rat

We studied the effects of peripheral and central administration of SCH 23390, a selective antagonist of dopamine D 1 receptors, on intracranial self-stimulation of the medial prefrontal cortex of the rat. Intraperitoneal injections of SCH 23390 produced a dose-related decrease in self-stimulation. Unilateral microinjections of SCH 23390 into the medial prefrontal cortex also produced a dose-related decrease in self-stimulation in the ipsilateral medial prefrontal cortex. However, self-stimulation of the contralateral, noninjected prefrontal cortex, used as control, was not affected. Together with previous data, the present results suggest that the dopamine neutotransmission involved in self-stimulation of the prefrontal cortex of the rat is mediated by dopamine D 1 receptors.

The appetite suppressant, d-fenfluramine, decreases self-stimulation at a feeding site in the lateral hypothalamus

In prior studies rats showed a relative shift from self-stimulation to escape (i.e., from reward to aversion) following a large meal, obesity or anorectic doses of insulin. Racemic fenfluramine, on the other hand, decreased both self-stimulation and escape suggesting it had a general behavior suppressant property. To avoid the depressive, antidopaminergic effects of the l-isomer, this study tested the d-isomer which is primarily serotonergic. Rats were screened for stimulation-induced feeding and then trained to self-stimulate with one lever in 5-min periods that alternated with 5-min periods of automatic stimulation from which the animal could escape with a different lever. d-Fenfluramine (1.5–4.5 mg/kg IP) caused a dose-related decrease in self-stimulation. Stimulation-escape was relatively unaffected. This is interpreted as a decrease in feeding reward due to d-fenfluramine.

Similar potencies of CCK-8 and its analogue BOC(Nle 28;Nle 31)CCK 27–33 on the self-stimulation behaviour both are antagonized by a newly synthesized cyclic CCK analogue

Neurons with co-localized cholecystokinin (CCK) and dopamine (DA) are present predominantly in the ventral tegmental area (VTA) and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopaminergic system can be avaluated by means of the intracranial self-stimulation behaviour (ICSS) on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of the CCK analogue BOC(Nle 28;Nle 31)CCK 27–33 (BDNL-CCK7) into a lateral ventricle decreased the electrical self-stimulation of the medial forebrain bundle. Nevertheless, this decrease in self-stimulation was steeper (immediately after the injection vs a delay of +/− 5–10 min.) than the CCK8-induced ICSS depletion. The intracerebroventricular (ICV) injection of 150 pmol and 1000 pmol BC-197 (BOC-D.Asp-Tyr(SO 3H)-Nle-D.Lys-Trp-Nle-Asp-Phe-NH 2) was inffective to modify the self-stimulation behaviour when administered alone while a 150 pmol BC-197 dosage was able to antagonize the decreasing effect of 150 pmol CCK-8 on ICSS. Nevertheless, a dosage 6 times as important, i.e. 1000 pmol BC-197, was needed to antagonize the depression induced by 150 pmol BDNL-CCK7 on ICSS behaviour. These results support the equipotence of BDNL-CCK7 to CCK-8 in decreasing the selfstimulation behaviour after their direct administration into the lateral ventricle. They further give evidence of the relevance of BC-197 in antagonizing the respective effects of both compounds on the ICSS.

Peptides and self-stimulation of the medial prefrontal cortex in the rat: Effects of intracerebral microinjections of substance P and cholecystokinin

The effects of intracerebral microinjections of substance P and cholecystokinin on self-stimulation of the medial prefrontal cortex of the rat were studied. Intracerebroventricular administration of substance P at doses of 2.5, 5, 10 and 20 micrograms produced a dose-related decrease in self-stimulation of the medial prefrontal cortex; spontaneous motor activity, measured as a control, was not affected. Unilateral microinjections into the medial prefrontal cortex of substance P at doses of 10 and 20 micrograms produced a decrease of self-stimulation of the ipsilateral side, but self-stimulation of the contralateral cortex, used as a control, was not affected. On the contrary, cholecystokinin in both intracerebroventricular administration at doses of 100, 200 and 400 ng, or intracortical microinjections into the medial prefrontal cortex at doses of 200, 400 and 800 ng, had no effect on self-stimulation of this cortical area. These results suggest that substance P, but not cholecystokinin, could be part of the neurochemical substrate underlying self-stimulation of the medial prefrontal cortex in the rat.

Effects of quipazine and of tryptamine on self-stimulation of median raphé nucleus and of lateral hypothalamus in rats

Separate groups of male Wistar rats were trained to lever press on a continuous reinforcement schedule under which behaviour was maintained by electrical stimulation of the median raphé nucleus (N = 6) or the lateral hypothalamus (N = 6). The effects of several doses of quipazine (2.5–7.1 mg/kg) and of tryptamine (10–80 mg/kg) were assessed with each group. Administration of quipazine resulted in a decrease of median raphé self-stimulation at 5.0 and 7.1 mg/kg. This compound had no statistically significant effect on lateral hypothalamic self-stimulation. Administration of tryptamine resulted in significant decreases in self-stimulation at both sites, however, whereas the effects of this drug were significant at 20, 40 and 80 mg/kg with median raphé self-stimulation, a significant decrease in lateral hypothalamic self-stimulation was only observed at 80 mg/kg. As baseline response rates differed in the two self-stimulation sites, a second group of animals with lateral hypothalamic sites (n = 6) were tested with quipazine (2.5–7.1 mg/kg) at an overall baseline response rate matched to that of the median raphé group. Although a tendency to decrease self-stimulation rates was found in this group, these results were not significant. These data suggest, therefore, that median raphé self-stimulation is more sensitive than lateral hypothalamic self stimulation to disruption by the effects of quipazine and tryptamine.

Lateralized decrease in self-stimulation induced by haloperidol in rats with unilateral 6-hydroxydopamine lesions

Rats with bilateral hypothalamic electrode placements which generated similar self-stimulation rate-intensity functions were subjected to unilateral injections of 6-hydroxydopamine (6-OHDA) into A 9 and A 10 areas. Following 12 weeks of postoperative recovery which was bilaterally symmetrical the rats were administered 0.1 mg/kg haloperidol. In sham- and vehicle-injected control rats the haloperidol produced bilaterally symmetrical decreases in self-stimulation. In the rats with 6-OHDA lesions the haloperidol effect was asymmetric with a much greater decrease in self-stimulation evident for electrode placements in the dopamine deficient hemisphere than for electrodes in the non-lesion hemisphere. Biochemical evaluation of the lesions indicated that dopamine was severely depleted in limbic and striatal forebrain areas. The combined use of a lesion with a pharmacological blockade of a neurotransmitter system appears to be an effective technique to distinguish reward versus performance effects of the transmitter on self-stimulation.

Electrical self-stimulation deficits in the anterior and posterior parts of the medial forebrain bundle after ibotenic acid lesion of the middle lateral hypothalamus

The aim of the present study was to analyse the involvement of the intrinsic neurons located in the middle lateral hypothalamus in electrical self-stimulation measured with electrodes in the anterior and posterior parts of the medial forebrain bundle. In rats without hypothalamic lesions, self-stimulation rates from both anterior and posterior electrodes were similar on either side of the brain. For all rats with ibotenic acid-induced lesions in the lateral hypothalamus, self-stimulation rates were lower with electrodes in the area of the lesion, while self-stimulation on the contralateral side was normal. In rats with electrodes in the anterior hypothalamus, the lesion produced a large deficit when stimulation was applied to the anterior electrode ipsilateral to the lesion. Only three rats showed a decrease in self-stimulation with stimulation of the posterior hypothalamic electrode ipsilateral to the lesion; self-stimulation of the other three rats was normal. These results suggest that self-stimulation in the anterior part of the medial forebrain bundle is supported by long fibers originating in the middle part of the lateral hypothalamus, while self-stimulation in the posterior part of the lateral hypothalamus can be influenced by another system not involved in reward processes observed in the rostral part of the medial forebrain bundle.

Apomorphine-induced facilitation of intracranial self-stimulation following dopamine denervation of the nucleus accumbens

Two groups of rats were trained to lever press for intracranial self-stimulation (ICSS) from electrodes aimed at the posterior lateral hypothalamus or at the region of the locus coeruleus. Following stabilization of baseline responding using descending rate/intensity functionsm,bilateral 6-hydroxydopamine (6-OHDA) lesions to the nucleus accumbens (N.Acc.) were performed. Subsequent injections of apomorphine (SC) resulted in significant increases in self-stimulation in both lesion groups and significant decreases in self-stimulation in both groups of sham operated animals. These results indicate that the destruction of the dopaminergic terminals in the nucleus accumbens results in a “supersensitive” enhancement of the ICSS stimulating properties of apomorphine regardless of the electrode placement. Both lesion groups also showed a pronounced increase in locomotor activity in photocell cages following treatment with the same dose of apomorphine. These results complement previous work showing that dopamine destruction affects ICSS regardless of electrode placement and support the hypothesis that the midbrain dopamine systems have a general response enabling role in reinforced behavior.

Rate dependent inhibition of self-stimulation by apomorphine

The effect of three doses of apomorphine 0.125, 0.25 and 0.5 were studied on self-stimulation generated by three levels of current intensity. Eight rats exhibited overall dose dependent decreases in self-stimulation obtained at the two lowest current intensities. Self-stimulation at the highest current intensity, however, was unaffected by even the highest dose level of apomorphine (0.5 mg/kg) despite typical signs of stereotypy exhibited by the rats in their home cages. Additionally, self-stimulation obtained under the 0.5 mg/kg dose of apomorphine underwent extinction when reinforcement was discontinued. Thus, brain stimulation can be an effective reinforcement when an animal is given a stereotypy inducing dose of apomorphine if the current intensity is of sufficient magnitude and if the response manipulandum is not compatible with stereotypic responses. These observations appear consistent with a dopaminergic involvement in the response rather than reinforcement aspect of self-stimulation.

Behavioral changes induced by basolateral amygdala self-stimulation

Rats given continuous access to rewarding stimulation of the posterior hypothalamus are able to maintain normal food and water intake despite high rates of self-stimulation. However, access to rewarding stimulation of the basolateral amygdala produced suppression of feeding and drinking followed by dramatic increases in emotionality and subsequent decreases in self-stimulation. These findings are considered with regard to the existing literature on basolateral amygdaloid lesions and stimulation.

Self-stimulation of the MFB or VTA after microinjection of haloperidol into the prefrontal cortex of the rat

Haloperidol, a dopamine receptor antagonist, was microinjected in doses of 12 or 24 μg into the prefrontal cortex of the rat. Its effects on self-stimulation of the ventral tegmental area (VTA) or the medial forebrain bundle (MFB) were examined. It was found that these injections failed to attenuate self-stimulation at either structure. However, when haloperidol was injected into the caudate-putamen complex, a decrease in self-stimulation occurred within these structures. These results suggest that dopamine in the medial prefrontal cortex is not necessarily a part of the neurochemical substrate underlying self-stimulation of the ventral tegmental area or medial forebrain bundle.

Effects of various inhibitors of tyrosine hydroxylase and dopamine beta-hydroxylase on rat self-stimulation after reserpine treatment.

The behavioral effects of low doses of the catecholamine (CA) synthesis inhibitor, alpha-methyl-p-tyrosine (alpha-MPT, 50 mg/kg i.p.), or the norepinephrine (NE) synthesis inhibitors (FLA-63, 15 mg/kg i.p., U-14624, 50 mg/kg i.p., or disulfiram 150 mg/kg i.p.) were studied in rats pretreated with reserpine (1 mg/kg i.p.) 24 h before. Rats were implanted either in the area ventralis tegmenti (AVT) or in the lateral hypothalamus (LH). The modifications of CA synthesis and endogenous CA levels were estimated in a parallel experiment. Reserpine treatment produced a slow decrease in self-stimulation (SS) rates during the first 12 h; SS rates were 85% of control values 24 h after reserpine treatment. Injection of alpha-MPT in reserpine-pretreated rats inhibited SS (85% decrease 3 h after administration either in AVT or LH rats), whereas dopamine beta-hydroxylase inhibition had no great effect on SS. The administration of very low doses of alpha-MPT (20 mg/kg i.p.) to rats treated with reserpine (24 h before) plus FLA-63 (1 h before) induced an important decrease in SS rates in AVT-implanted rats only. The major conclusion is that dopaminergic neurons seem to be involved in AVT and LH SS. The last experiment suggests the involvement of a balance between dopaminergic and noradrenergic neurons in AVT SS.