The effects of quinpirole in eliciting 50 kHz calls from the rat nucleus accumbens /

Fifty kHz rat vocalizations are theorized to reflect a positive affective state, and index the reward value of stimuli (Knutson, Burgdorf & Panksepp, 2002; Panksepp & Burgdorf, 2003; Brudzynski,2005). Previous studies have identified the neurochemical substrate of this behaviour to be dependent on dopaminergic activity at the nucleus accumbens shell (Burgdorf, Knutson, Panksepp & Ikemoto, 2001; Thompson, Leonard & Brudzynski, 2006). The utilization of d-amphetamine (a non-selective dopamine agonist) in these studies does not address the specific dopamine receptor types involved. The present study aims to identify the role of the D2- like family of receptors in the nucleus accumbens shell in the production of 50 kHz vocalizations in adult rats. Single injections of quinpirole in a saline vehicle were administered to the nucleus accumbens shell of 57 rats, and the number of 50 kHz vocalizations were recorded. An inverted V-shaped relationship was found between quinpirole dose (0.5 ~g, 3 ~g, 6 ~g, 1 0 ~g and 20 ~g, all in 0.2~1 saline) and the mean number of 50 kHz calls produced. Quinpirole successfully elicited significantly more 50 kHz calls than did a saline control at the 6 ~g dose, as did 7 ~g/0.2 ~l of d-amphetamine injections into the same brain site. To test whether a selective D2 antagonist could reverse elicited 50 kHz calling, double injections were given that used either saline or raclopride as a pretreatment before quinpirole injections. Saline followed by 6 ~g/0.2 ~l of quinpirole elicited significantly more 50 kHz vocalizations than did a double injection of saline, while pretreatment with an equimolar dose of raclopride reduced elicited calls to control levels. Raclopride was also used as a pretreatment of 7 ~g/0.2 ~l d-amphetamine, which elicited significantly fewer 50 kHz vocalizations than saline followed by amphetamine, replicating the finding of Thompson, Leonard & Brudzynski (2006).Subcutaneous injections of 0.5 mg/kg and 1.5 mg/kg of quinpirole produced a similar number of 50 kHz vocalizations as subcutaneous injection of saline. Wider dose ranges may be explored in fiiture research. Thus, direct activation of the Da-like receptors in the nucleus accumbens shell was sufficient to elicit 50 kHz vocalizations in adult rats, an effect which was reversed with selective local antagonism of Da-like receptors. The Da-like receptor family also appears necessary for pharmacological activation of 50 kHz calling, as d-amphetamine was no longer able to effectively elicit these vocalizations from the nucleus accumbens shell when the Da-receptor family was antagonized with raclopride. The acoustic parameters of elicited vocalizations remained typical of rat 50 kHz calls. Detailed analyses of the acoustic characteristics of elicited calls indicated significant increases in call duration and peak frequency across drug injection groups, particularly among quinpirole dose groups. The implications of these findings are not yet clear, but may represent an important direction for future research into the coding of semiotic content into affective signals in rats.

Effects of low doses of quinpirole on production of 50 kHz vocalizations in Wistar rats

Rats emit two distinct types of ultrasonic vocalizations in adulthood: 22 kHz (aversive situation), and 50 kHz calls (appetitive situation). The present project is focussed on pharmacological studies of 50 kHz vocalizations. The 50 kHz calls are elicited from dopaminergic activation in the meso limbic pathway and are emitted in such appetitive situations as social contact(s), sexual encounters, food reward, etc. Eighty-five male rats were stereotaxically implanted with bilateral guide cannulae in the nucleus accumbens shell (A= 9.7, L= 1.2, V= 6.7). Quinpirole, a D2/D3 dopaminergic agonist, was injected in low doses to the nucleus accumbens shell in an attempt to elicit 50 kHz vocalizations. A dose response was obtained for the low dose range of quinpirole for six doses: 0.025 Jlg, 0.06 Jlg, 0.12 Jlg, 0.25 Jlg, 0.5 Jlg, and 1.0 Jlg. It was found that only application of the 0.25 Jlg dose of quinpirole and the 7 Jlg dose of amphetamine (positive control) significantly increased the total number of 50 kHz calls (p < 0.006 and p < 0.004 respectively); and particularly significantly increased the frequency modulated type of these calls (p < 0.01, and p < 0.006 respectively). In a double injection procedure, the dose of 0.25 Jlg quinpirole was antagonized with raclopride (D2 antagonist) or U99194A maleate (D3 antagonist) in an attempt to antagonize the response. The 0.25 Jlg dose of quinpirole was successfully antagonized by pre-treatment with an equimolar dose of U99194A maleate (p < 0.008) but not with raclopride. The 7Jlg amphetamine response was also antagonized with an equimolar dose of raclopride. Based on these results, it seems that low doses of quinpirole, particularly the 0.25 Jlg dose, are capable of increasing 50 kHz vocalizations in rats and do so by activation of the D3 dopamine receptor. This is not a biphasic response as seen with locomotor studies. Also noteworthy is the increase in frequency modulated 50 kHz calls elicited by the 0.25 Jlg dose of quinpirole indicating a possible increase in positive affect.

Brochure - Hydro Golden Jubilee - (1906-1956) 50 Years of Progress

A brochure for Ontario Hydro marking the 50 year Jubilee. The brochure also describes the change over from 25 cycle to 60 cycle service. A map details the areas that have made the change to 60 cycle power and those still waiting to transition. There is also a section of eight questions and answers concerning the change to 60 cycle power.

Boston Gazette, 13 December 1813 (vol. 39, no. 50) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812. Issue for Dec. 13, 1813: much of the front page & a portion of page 2 are taken up with the "President's Message" which is signed by him in type at its conclusion: James Madison. Obviously much of the focus of his speech is with the on-going War of 1812 including mention of some significant battles such as Lake Erie, etc.

The War, 31 May 1814 (vol. 2, no. 50, whole no. 102) - Newspaper

Volumes of interest were published between 1812 and 1815 with articles about the War of 1812.

Investigation of the role of the nucleus accumbens in amphetamine-induced 50 kHz ultrasonic vocalizations in the rat

There is extensive evidence that the mesolimbic dopamine system underlies the production of 50 kHz ultrasonic vocalizations in rats. In particular, the shell of the nucleus accumbens is associated with generation of frequency modulated 50 kHz calls (a specific type of 50 kHz call which can be subdivided into various subtypes). There is also evidence that amphetamine administered systemically preferentially increases the proportion of trill and step calls compared to other frequency modulated 50 kHz subtypes. The purpose of this study was to investigate the effect of drug administration route and the role of the nucleus accumbens shell in amphetamine-induced 50 kHz call profile in the rat. Three experiments investigated this by using subcutaneous and intra-accumbens microinjections of amphetamine, as well as procaine (a local anesthetic) blockade of the nucleus accumbens. Ultrasonic vocalizations were recorded digitally from 24 rats and were analysed for sonographic structure based on general call parameters. The results of the three experiments were partially supportive of the hypotheses. Systemic amphetamine was found to induce greater bandwidth in 50 kHz calling compared to spontaneous calls in a vehicle condition. Systemic amphetamine was also found to preferentially increase the proportion of trill and step subtypes compared to vehicle. Moreover, there was no difference in the proportions of 50 kHz subtypes resulting from intracerebral or systemic application of amphetamine. There was, however, a significant difference for bandwidth, with systemic amphetamine inducing greater bandwidth over intraaccumbens application. Procaine blockade of the nucleus accumbens shell paired with subcutaneous amphetamine produced no difference in bandwidth of calls compared with those after a vehicle pre-treatment similarly paired. There was no reduction in the proportions of trill and step 50 kHz subtypes as well, with the procaine condition showing significantly greater proportion of step calls. The results of the study support a role for the iii nucleus accumbens shell in the amphetamine-induced changes on 50 kHz call profile. They also indicate there are more regions and pathways involved in generating 50 kHz calls than the projections from the ventral tegmental area to the nucleus accumbens. The implications of this work are that frequency modulated 50 kHz subtypes may be generated by distinct neurophysiological mechanisms and may represent a profitable avenue for investigating different circuits of 50 kHz call categories in the rat.

HG 226.50-226.60 Thin Section

Dark brown sediment with manly small sized clasts. Some medium and large clasts also present. Clasts range from sub-angular to sub-rounded. Lineations can be seen throughout the sample. Minor patches of clay/organic rich domains can also be seen as well as minor grain stacking.

HG 244.40-244.50-A Thin Section

Dark brown sediment with sub-angular to sub-rounded clasts. Rotation structures and lineations are common. Clasts ranging from small to large in size. Many large grains are fractured. Minor amounts of grain stacking and crushing can be seen. A few clay and organic rich domains can be seen.

HG 421.50-421.60

Light brown sediment with clasts that range from small to large in size. The clast shape ranges from sub-angular to sub-rounded. Lineations and rotation structures are abundant in this sample. Edge-to-edge grain crushing is present as well. There are areas of light and dark sediment throughout the sample. A few comet structures can also be seen.

HG 437.50-437.55

Light brown sample with clasts ranging from small to large. The clast shape ranges from sub-angular to sub-rounded. Grain crushing is common in this sample and mainly involves the larger clasts. Many grains are also crushed into one another. The larger grains are also fractured. Lineations and faint water escape structures can also be seen. This sample also contains a finer grained domain, darker in colour.

HG 18.50-18.55

This sample contains grains that range from small to large in size. The clast shape ranges from angular to rounded. Many grains are fractured and grain crushing is commonly seen. A few necking structures and rotation structures can also be seen.

HG 46.40-46.50

Brown sediment with areas of clay rich material (darker brown). Clasts range from small to large in size. Clast shape ranges from angular to rounded. Rotation structures and necking structures were abundant in this sample. Some lineations and grain stacking can also be seen throughout the sample.

59.40-59.50

Brown sediment with clasts ranging from small to medium in size. Clast shape ranges from angular to sub-rounded. Lineations are common in this sample along with grain crushing. A few comet structures can also be seen.

HG 70.40-70.50

Dark brown sediment with clasts ranging from small to large in size. Clast shape ranges from angular to sub-rounded. Lineations and comet structures can commonly be seen throughout the sample. Some rotation structures and grain crushing can also be seen in varying amounts.